Publications

@article{pmid39204272,

title = {BacSPaD: A Robust Bacterial Strains' Pathogenicity Resource Based on Integrated and Curated Genomic Metadata},

author = {Sara Ribeiro and Guillaume Chaumet and Karine Alves and Julien Nourikyan and Lei Shi and Jean-Pierre Lavergne and Ivan Mijakovic and Simon de Bernard and Laurent Buffat},

doi = {10.3390/pathogens13080672},

issn = {2076-0817},

year  = {2024},

date = {2024-08-01},

urldate = {2024-08-01},

journal = {Pathogens},

volume = {13},

number = {8},

abstract = {The vast array of omics data in microbiology presents significant opportunities for studying bacterial pathogenesis and creating computational tools for predicting pathogenic potential. However, the field lacks a comprehensive, curated resource that catalogs bacterial strains and their ability to cause human infections. Current methods for identifying pathogenicity determinants often introduce biases and miss critical aspects of bacterial pathogenesis. In response to this gap, we introduce BacSPaD (Bacterial Strains' Pathogenicity Database), a thoroughly curated database focusing on pathogenicity annotations for a wide range of high-quality, complete bacterial genomes. Our rule-based annotation workflow combines metadata from trusted sources with automated keyword matching, extensive manual curation, and detailed literature review. Our analysis classified 5502 genomes as pathogenic to humans (HP) and 490 as non-pathogenic to humans (NHP), encompassing 532 species, 193 genera, and 96 families. Statistical analysis demonstrated a significant but moderate correlation between virulence factors and HP classification, highlighting the complexity of bacterial pathogenicity and the need for ongoing research. This resource is poised to enhance our understanding of bacterial pathogenicity mechanisms and aid in the development of predictive models. To improve accessibility and provide key visualization statistics, we developed a user-friendly web interface.},

keywords = {medical data, omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38510150,

title = {Exogenous IL-2 delays memory precursors generation and is essential for enhancing memory cells effector functions},

author = {Shaoying Wang and Margaux Prieux and Simon de Bernard and Maxence Dubois and Daphne Laubreton and Sophia Djebali and Manon Zala and Christophe Arpin and Laurent Genestier and Yann Leverrier and Olivier Gandrillon and Fabien Crauste and Wenzheng Jiang and Jacqueline Marvel},

doi = {10.1016/j.isci.2024.109411},

issn = {2589-0042},

year  = {2024},

date = {2024-04-01},

urldate = {2024-04-01},

journal = {iScience},

volume = {27},

number = {4},

pages = {109411},

abstract = {To investigate the impact of paracrine IL-2 signals on memory precursor (MP) cell differentiation, we activated CD8 T cell  in the presence or absence of exogenous IL-2 (ex-IL-2). We assessed memory differentiation by transferring these cells into virus-infected mice. Both conditions generated CD8 T cells that participate in the ongoing response and gave rise to similar memory cells. Nevertheless, when transferred into a naive host, T cells activated with ex-IL-2 generated a higher frequency of memory cells displaying increased functional memory traits. Single-cell RNA-seq analysis indicated that without ex-IL-2, cells rapidly acquire an MP signature, while in its presence they adopted an effector signature. This was confirmed at the protein level and in a functional assay. Overall, ex-IL-2 delays the transition into MP cells, allowing the acquisition of effector functions that become imprinted in their progeny. These findings may help to optimize the generation of therapeutic T cells.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid38015712,

title = {Chronological aging impacts abundance, function and microRNA content of extracellular vesicles produced by human epidermal keratinocytes},

author = {Taku Nedachi and Christelle Bonod and Julie Rorteau and Wafae Chinoune and Yuri Ishiuchi and Sandrine Hughes and Benjamin Gillet and Nicolas Bechetoille and Dominique Sigaudo-Roussel and Jérôme Lamartine},

doi = {10.18632/aging.205245},

issn = {1945-4589},

year  = {2023},

date = {2023-11-01},

urldate = {2023-11-01},

journal = {Aging (Albany NY)},

volume = {15},

number = {22},

pages = {12702--12722},

abstract = {The disturbance of intercellular communication is one of the hallmarks of aging. The goal of this study is to clarify the impact of chronological aging on extracellular vesicles (EVs), a key mode of communication in mammalian tissues. We focused on epidermal keratinocytes, the main cells of the outer protective layer of the skin which is strongly impaired in the skin of elderly. EVs were purified from conditioned medium of primary keratinocytes isolated from infant or aged adult skin. A significant increase of the relative number of EVs released from aged keratinocytes was observed whereas their size distribution was not modified. By small RNA sequencing, we described a specific microRNA (miRNA) signature of aged EVs with an increase abundance of miR-30a, a key regulator of barrier function in human epidermis. EVs from aged keratinocytes were found to be able to reduce the proliferation of young keratinocytes, to impact their organogenesis properties in a reconstructed epidermis model and to slow down the early steps of skin wound healing in mice, three features observed in aged epidermis. This work reveals that intercellular communication mediated by EVs is modulated during aging process in keratinocytes and might be involved in the functional defects observed in aged skin.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37347665,

title = {The multi-level regulation of clownfish metamorphosis by thyroid hormones},

author = {Natacha Roux and Saori Miura and Mélanie Dussenne and Yuki Tara and Shu-Hua Lee and Simon de Bernard and Mathieu Reynaud and Pauline Salis and Agneesh Barua and Abdelhay Boulahtouf and Patrick Balaguer and Karine Gauthier and David Lecchini and Yann Gibert and Laurence Besseau and Vincent Laudet},

doi = {10.1016/j.celrep.2023.112661},

issn = {2211-1247},

year  = {2023},

date = {2023-06-01},

urldate = {2023-06-01},

journal = {Cell Rep},

volume = {42},

number = {7},

pages = {112661},

abstract = {Most marine organisms have a biphasic life cycle during which pelagic larvae transform into radically different juveniles. In vertebrates, the role of thyroid hormones (THs) in triggering this transition is well known, but how the morphological and physiological changes are integrated in a coherent way with the ecological transition remains poorly explored. To gain insight into this question, we performed an integrated analysis of metamorphosis of a marine teleost, the false clownfish (Amphiprion ocellaris). We show how THs coordinate a change in color vision as well as a major metabolic shift in energy production, highlighting how it orchestrates this transformation. By manipulating the activity of liver X regulator (LXR), a major regulator of metabolism, we also identify a tight link between metabolic changes and metamorphosis progression. Strikingly, we observed that these regulations are at play in the wild, explaining how hormones coordinate energy needs with available resources during the life cycle.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{Sanlaville2023.02.15.528594,

title = {CD4 T cells and neutrophils contribute to epithelial-mesenchymal transition in breast cancer},

author = {Amélien Sanlaville and Aurélien Voissière and Dominique Poujol and Margaux Hubert and Suzanne André and Clémence Perret and Jean-Philippe Foy and Nadège Goutagny and Marine Malfroy and Isabelle Durand and Marie Châlons-Cottavoz and Jenny Valladeau-Guilemond and Pierre Saintigny and Alain Puisieux and Christophe Caux and Marie-Cécile Michallet and Isabelle Puisieux and Nathalie Bendriss-Vermare},

url = {https://www.biorxiv.org/content/early/2023/02/15/2023.02.15.528594},

doi = {10.1101/2023.02.15.528594},

year  = {2023},

date = {2023-02-15},

urldate = {2023-01-01},

journal = {bioRxiv},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Epithelial-mesenchymal transition (EMT) is a central oncogenic mechanism, contributing both to transformation and metastatic dissemination. Inflammation and innate immune cells are known to favor EMT induction, but the role of adaptive immunity still remains unclear. Using an original murine mammary tumor model in immune cell subpopulation depletion experiments, we demonstrated that tumor cells maintain their epithelial phenotype in mice deficient for adaptive immune response, but undergo EMT in the presence of T-cells. This phenotypic conversion involves the major contribution of CD4 T cells, but not CD8 T cells nor B cells, undoubtedly demonstrating the pro-EMT role of CD4 T cells specifically among adaptive immune cells. Moreover, combined intra-tumor immune infiltrate and transcriptomic analyses of murine mammary tumors with various EMT phenotype revealed an inverse correlation between mesenchymal tumor cell and intratumoral neutrophil proportions, due to the reduced ability of mesenchymal cells to recruit neutrophils. Last, selective in vivo depletion of neutrophils and transcriptomic analysis of human breast tumor cohorts demonstrated the pro-EMT role of neutrophils and suggest a cooperation with CD4 T cells in EMT promotion. Collectively, our data highlight a novel mechanism of EMT regulation by both innate and adaptive immune compartments.Competing Interest StatementThe authors have declared no competing interest.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36832246,

title = {Performance of T-Track TB, a Novel Dual Marker RT-qPCR-Based Whole-Blood Test for Improved Detection of Active Tuberculosis},

author = {Johannes P Meier and Selina Möbus and Florian Heigl and Alexandra Asbach-Nitzsche and Hans Helmut Niller and Annelie Plentz and Korkut Avsar and Marion Heiß-Neumann and Bernhard Schaaf and Uwe Cassens and Bernd Seese and Daniel Teschner and Sabin Handzhiev and Uwe Graf and Christoph Lübbert and Monika Steinmaurer and Konstantina Kontogianni and Christoph Berg and Andreas Maieron and Stefan H Blaas and Ralf Wagner and Ludwig Deml and Sascha Barabas},

doi = {10.3390/diagnostics13040758},

issn = {2075-4418},

year  = {2023},

date = {2023-02-01},

urldate = {2023-02-01},

journal = {Diagnostics (Basel)},

volume = {13},

number = {4},

abstract = {Tuberculosis (TB) is one of the leading causes of death by an infectious disease. It remains a major health burden worldwide, in part due to misdiagnosis. Therefore, improved diagnostic tests allowing the faster and more reliable diagnosis of patients with active TB are urgently needed. This prospective study examined the performance of the new molecular whole-blood test T-Track TB, which relies on the combined evaluation of  and  mRNA levels, and compared it to that of the QuantiFERON-TB Gold Plus (QFT-Plus) enzyme-linked immunosorbent assay (ELISA). Diagnostic accuracy and agreement analyses were conducted on the whole blood of 181 active TB patients and 163 non-TB controls. T-Track TB presented sensitivity of 94.9% and specificity of 93.8% for the detection of active TB vs. non-TB controls. In comparison, the QFT-Plus ELISA showed sensitivity of 84.3%. The sensitivity of T-Track TB was significantly higher ( < 0.001) than that of QFT-Plus. The overall agreement of T-Track TB with QFT-Plus to diagnose active TB was 87.9%. Out of 21 samples with discordant results, 19 were correctly classified by T-Track TB while misclassified by QFT-Plus (T-Track TB-positive/QFT-Plus-negative), and two samples were misclassified by T-Track TB while correctly classified by QFT-Plus (T-Track TB-negative/QFT-Plus-positive). Our results demonstrate the excellent performance of the T-Track TB molecular assay and its suitability to accurately detect TB infection and discriminate active TB patients from non-infected controls.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36007550,

title = {MXD4/MAD4 Regulates Human Keratinocyte Precursor Fate},

author = {Julien Coutier and Frédéric Auvré and Gilles Lemaître and Jean-Jacques Lataillade and Jean-François Deleuze and Paul-Henri Roméo and Michèle T Martin and Nicolas O Fortunel},

doi = {10.1016/j.jid.2022.07.020},

issn = {1523-1747},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {J Invest Dermatol},

volume = {143},

number = {1},

pages = {105--114.e12},

abstract = {Deciphering the pathways that regulate human epidermal precursor cell fate is necessary for future developments in skin repair and graft bioengineering. Among them, characterization of pathways regulating the keratinocyte (KC) precursor immaturity versus differentiation balance is required for improving the efficiency of KC precursor ex vivo expansion. In this study, we show that the transcription factor MXD4/MAD4 is expressed at a higher level in quiescent KC stem/progenitor cells located in the basal layer of human epidermis than in cycling progenitors. In holoclone KCs, stable short hairpin-RNA‒mediated decreased expression of MXD4/MAD4 increases MYC expression, whose modulation increases the proliferation of KC precursors and maintenance of their clonogenic potential and preserves the functionality of these precursors in three-dimensional epidermis organoid generation. Altogether, these results characterize MXD4/MAD4 as a major piece of the stemness puzzle in the human epidermis KC lineage and pinpoint an original avenue for ex vivo expansion of human KC precursors.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36482098,

title = {RNA-Seq comparative study reveals molecular effectors linked to the resistance of Pinna nobilis to Haplosporidium pinnae parasite},

author = {Pauline Salis and Claire Peyran and Titouan Morage and Simon de Bernard and Julien Nourikyan and Stéphane Coupé and Robert Bunet and Serge Planes},

doi = {10.1038/s41598-022-25555-x},

issn = {2045-2322},

year  = {2022},

date = {2022-12-01},

urldate = {2022-12-01},

journal = {Sci Rep},

volume = {12},

number = {1},

pages = {21229},

abstract = {With the intensification of maritime traffic, recently emerged infectious diseases have become major drivers in the decline and extinction of species. Since 2016, mass mortality events have decimated the endemic Mediterranean Sea bivalve Pinna nobilis, affecting ca. 100% of individuals. These events have largely been driven by Haplosporidium pinnae's infection, an invasive species which was likely introduced by shipping. While monitoring wild populations of P. nobilis, we observed individuals that survived such a mass mortality event during the summer of 2018 (France). We considered these individuals resistant, as they did not show any symptoms of the disease, while the rest of the population in the area was devastated. Furthermore, the parasite was not detected when we conducted a PCR amplification of a species-specific fragment of the small subunit ribosomal DNA. In parallel, the transcriptomic analysis showed evidence of some parasite RNA indicating that the resistant individuals had been exposed to the parasite without proliferating. To understand the underlying mechanisms of resistance in these individuals, we compared their gene expression with that of susceptible individuals. We performed de novo transcriptome assembly and annotated the expressed genes. A comparison of the transcriptomes in resistant and susceptible individuals highlighted a gene expression signature of the resistant phenotype. We found significant differential expressions of genes involved in immunity and cell architecture. This data provides the first insights into how individuals escape the pathogenicity associated with infection.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36065187,

title = {CD8 memory precursor cell generation is a continuous process},

author = {Helena Todorov and Margaux Prieux and Daphne Laubreton and Matteo Bouvier and Shaoying Wang and Simon de Bernard and Christophe Arpin and Robrecht Cannoodt and Wouter Saelens and Arnaud Bonnaffoux and Olivier Gandrillon and Fabien Crauste and Yvan Saeys and Jacqueline Marvel},

doi = {10.1016/j.isci.2022.104927},

issn = {2589-0042},

year  = {2022},

date = {2022-09-01},

urldate = {2022-09-01},

journal = {iScience},

volume = {25},

number = {9},

pages = {104927},

abstract = {In this work, we studied the generation of memory precursor cells following an acute infection by analyzing single-cell RNA-seq data that contained CD8 T cells collected during the postinfection expansion phase. We used different tools to reconstruct the developmental trajectory that CD8 T cells followed after activation. Cells that exhibited a memory precursor signature were identified and positioned on this trajectory. We found that these memory precursors are generated continuously with increasing numbers arising over time. Similarly, expression of genes associated with effector functions was also found to be raised in memory precursors at later time points. The ability of cells to enter quiescence and differentiate into memory cells was confirmed by BrdU pulse-chase experiment . Analysis of cell counts indicates that the vast majority of memory cells are generated at later time points from cells that have extensively divided.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35184302,

title = {Gene profiling reveals a contact allergy signature in most positive Amerchol L-101 patch test reactions},

author = {Linda Ljungberg Silic and Marine-Alexia Lefevre and Ola Bergendorff and Simon De Bernard and Julien Nourikyan and Laurent Buffat and Audrey Nosbaum and Magnus Bruze and Jean-François Nicolas and Cecilia Svedman and Marc Vocanson},

doi = {10.1111/cod.14077},

issn = {1600-0536},

year  = {2022},

date = {2022-07-01},

urldate = {2022-07-01},

journal = {Contact Dermatitis},

volume = {87},

number = {1},

pages = {40--52},

abstract = {BACKGROUND: Diagnosis of contact allergy (CA) to Amerchol L-101 (AL-101), a marker for lanolin allergy, is problematic. Positive patch test reactions are frequently doubtful or weakly positive and difficult to associate with clinical relevance.



OBJECTIVE: To gain further insight on the allergic or irritant nature of skin reactions induced by AL-101 patch test.



METHODS: We re-tested in a dose-response fashion, 10 subjects with AL-101 CA and performed comprehensive transcriptomic analysis (gene arrays, quantitative real-time polymerase chain reaction [qRT-PCR]) of samples of their skin reactions.



RESULTS: Eight of the 10 CA subjects reacted positively upon re-test, whereas two did not react. Most of AL-101 positive patch tests expressed an allergy signature with strong activation of gene modules associated with adaptive immunity and downregulation of cornification pathway genes. In addition, the breadth of gene modulation correlated with the magnitude of patch test reactions and the concentration of AL-101 applied. However, we observed that some of the positive patch test reactions to AL-101 expressed no/few allergy biomarkers, suggesting the induction of an irritant skin inflammation in these samples.



CONCLUSIONS: This study confirms that AL-101 is an allergen that can cause both contact allergy and contact irritation. Our results also highlight that molecular profiling might help to strengthen clinical diagnosis.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{Roux2022.03.04.482938,

title = {The multi-level regulation of clownfish metamorphosis by thyroid hormones},

author = {Natacha Roux and Saori Miura and Mélanie Dussene and Yuki Tara and Fiona Lee and Simon Bernard and Mathieu Reynaud and Pauline Salis and Agneesh Barua and Abdelhay Boulahtouf and Patrick Balaguer and Karine Gauthier and David Lecchini and Yann Gibert and Laurence Besseau and Vincent Laudet},

url = {https://www.biorxiv.org/content/early/2022/03/04/2022.03.04.482938},

doi = {10.1101/2022.03.04.482938},

year  = {2022},

date = {2022-03-04},

urldate = {2022-01-01},

journal = {bioRxiv},

publisher = {Cold Spring Harbor Laboratory},

abstract = {Most marine organisms have a biphasic life cycle during which a pelagic larva is transformed into a radically different juvenile. In vertebrates the role of thyroid hormones (TH) in triggering this transition is well known, but how the morphological and physiological changes are integrated in a coherent way with the ecological transition remains poorly explored. To gain insight into this question, we performed an integrative analysis of metamorphosis of a marine teleost, the clownfish Amphiprion ocellaris. We reveal how TH coordinate a change in color vision as well as a major metabolic shift in energy production, hence highlighting its central integrative role in regulating this transformation. By manipulating the activity of LXR, a major regulator of metabolism, we also reveal a tight link between metabolic changes and metamorphosis progression. Strikingly, we observed that these regulations are at play in the wild revealing how hormones coordinate energy needs with available resources during life cycle.Competing Interest StatementThe authors have declared no competing interest.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34286840,

title = {Therapeutic siRNAs Targeting the JAK/STAT Signalling Pathway in Inflammatory Bowel Diseases},

author = {Flora Clément and Adrien Nougarède and Stéphanie Combe and Frédérique Kermarrec and Arindam K Dey and Patricia Obeid and Arnaud Millet and Fabrice P Navarro and Patrice N Marche and Eric Sulpice and Xavier Gidrol},

doi = {10.1093/ecco-jcc/jjab129},

issn = {1876-4479},

year  = {2022},

date = {2022-02-01},

urldate = {2022-02-01},

journal = {J Crohns Colitis},

volume = {16},

number = {2},

pages = {286--300},

abstract = {BACKGROUND AND AIMS: Inflammatory bowel diseases are highly debilitating conditions that require constant monitoring and life-long medication. Current treatments are focused on systemic administration of immunomodulatory drugs, but they have a broad range of undesirable side-effects. RNA interference is a highly specific endogenous mechanism that regulates the expression of the gene at the transcript level, which can be repurposed using exogenous short interfering RNA [siRNA] to repress expression of the target gene. While siRNA therapeutics can offer an alternative to existing therapies, with a high specificity critical for chronically administrated drugs, evidence of their potency compared to chemical kinase inhibitors used in clinics is still lacking in alleviating an adverse inflammatory response.



METHODS: We provide a framework to select highly specific siRNA, with a focus on two kinases strongly involved in pro-inflammatory diseases, namely JAK1 and JAK3. Using western-blot, real-time quantitative PCR and large-scale analysis, we assessed the specificity profile of these siRNA drugs and compared their efficacy to the most recent and promising kinase inhibitors for Janus kinases [Jakinibs], tofacitinib and filgotinib.



RESULTS: siRNA drugs can reach higher efficiency and selectivity at lower doses [5 pM vs 1 µM] than Jakinibs. Moreover, JAK silencing lasted up to 11 days, even with 6 h pulse transfection.



CONCLUSIONS: The siRNA-based drugs developed hold the potential to develop more potent therapeutics for chronic inflammatory diseases.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35464449b,

title = {Dichotomy in Neutralizing Antibody Induction to Peptide-Conjugated Vaccine in Squalene Emulsion Contrast With Aluminum Hydroxide Formulation},

author = {Olivia Bonduelle and Chloé Chaudesaigues and Monica Tolazzi and Ehsan Suleiman and Simon de Bernard and Karine Alves and Julien Nourikyan and Mylene Bohec and Laura G Baudrin and Dietmar Katinger and Patrice Debré and Gabriella Scarlatti and Vincent Vieillard and Behazine Combadière},

doi = {10.3389/fimmu.2022.848571},

issn = {1664-3224},

year  = {2022},

date = {2022-01-01},

urldate = {2022-01-01},

journal = {Front Immunol},

volume = {13},

pages = {848571},

abstract = {W614A-3S peptide is a modified 3S motif of the HIV-gp41 (mutation W614A). We previously detected the presence of natural neutralizing antibodies directed against W614A-3S peptide (NAbs) in long-term non-progressor HIV patients. Here, we compared the efficacy of W614A-3S peptide formulated in either squalene emulsion (SQE) or in aluminum hydroxide (Alum) in inducing broadly-NAbs (bNAbs). Rabbit and mouse models were used to screen the induction of bNAbs following 4 immunizations. SQE was more efficient than Alum formulation in inducing W614A-3S-specific bNAbs with up to 67%-93% of HIV strains neutralized. We then analyzed the quality of peptide-specific murine B cells by single-cell gene expression by quantitative reverse transcription-PCR and single-cell V(D)J sequencing. We found more frequent germinal center B cells in SQE than in Alum, albeit with a different gene expression profile. The V(D)J sequencing of W614A-3S-specific BCR showed significant differences in BCR sequences and validates the dichotomy between adjuvant formulations. All sixteen BCR sequences which were cloned were specific of peptide. Adjuvant formulations of W614A-3S-peptide-conjugated immunogen impact the quantity and quality of B cell immune responses at both the gene expression level and BCR sequence.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34174113,

title = {Unique molecular signatures typify skin inflammation induced by chemical allergens and irritants},

author = {Marine-Alexia Lefevre and Audrey Nosbaum and Aurore Rozieres and Vanina Lenief and Amandine Mosnier and Angèle Cortial and Margaux Prieux and Simon De Bernard and Julien Nourikyan and Pierre-Emmanuel Jouve and Laurent Buffat and Florence Hacard and Marie-Christine Ferrier-Lebouedec and Pauline Pralong and Charles Dzviga and Anne Herman and Marie Baeck and Jean-François Nicolas and Marc Vocanson},

doi = {10.1111/all.14989},

issn = {1398-9995},

year  = {2021},

date = {2021-12-01},

urldate = {2021-12-01},

journal = {Allergy},

volume = {76},

number = {12},

pages = {3697--3712},

abstract = {BACKGROUND: Skin exposure to chemicals may induce an inflammatory disease known as contact dermatitis (CD). Distinguishing the allergic and irritant forms of CD often proves challenging in the clinic.



METHODS: To characterize the molecular signatures of chemical-induced skin inflammation, we conducted a comprehensive transcriptomic analysis on the skin lesions of 47 patients with positive patch tests to reference contact allergens and nonallergenic irritants.



RESULTS: A clear segregation was observed between allergen- and irritant-induced gene profiles. Distinct modules pertaining to the epidermal compartment, metabolism, and proliferation were induced by both contact allergens and irritants; whereas only contact allergens prompted strong activation of adaptive immunity, notably of cytotoxic T-cell responses. Our results also confirmed that: (a) unique pathways characterize allergen- and irritant-induced dermatitis; (b) the intensity of the clinical reaction correlates with the magnitude of immune activation. Finally, using a machine-learning approach, we identified and validated several minimal combinations of biomarkers to distinguish contact allergy from irritation.



CONCLUSION: These results highlight the value of molecular profiling of chemical-induced skin inflammation for improving the diagnosis of allergic versus irritant contact dermatitis.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33973663,

title = {Low-Level Light Therapy Downregulates Scalp Inflammatory Biomarkers in Men With Androgenetic Alopecia and Boosts Minoxidil 2% to Bring a Sustainable Hair Regrowth Activity},

author = {Yann F Mahe and Ahsène Cheniti and Charlotte Tacheau and Rosaria Antonelli and Lien Planard-Luong and Simon de Bernard and Laurent Buffat and Philippe Barbarat and Leila Kanoun-Copy},

doi = {10.1002/lsm.23398},

issn = {1096-9101},

year  = {2021},

date = {2021-11-01},

urldate = {2021-11-01},

journal = {Lasers Surg Med},

volume = {53},

number = {9},

pages = {1208--1219},

abstract = {BACKGROUND AND OBJECTIVES: Low-level light therapies using visible to infrared light are known to activate several cellular functions, such as adenosine triphosphate and nitric oxide synthesis. However, few clinical observations report its biological consequences for skin and scalp homeostasis. Since scalp inflammation was recognized as a potential physiological obstacle to the efficacy of the reference hair regrowth drug Minoxidil in vivo and since perifollicular inflammation is the hallmark of about 50%-70% follicular units in androgenetic alopecia, we decided to investigate whether the anti-inflammatory activity of LLLT/GentleWaves® device were assigned to L'Oréal by Light BioScience L.L.C., Virginia Beach, VA (US) could enhance hair regrowth activity of Minoxidil.



STUDY DESIGN/MATERIALS AND METHODS: We conducted a first experimental clinical study on 64 men with androgenetic alopecia using LLLT/GentleWaves®, 590-nm predominant wavelength 70 seconds, specifically pulsed once per day, for 3 days, and we performed a whole-genome analysis of treated scalp biopsies. In a second clinical study, including 135 alopecic volunteers, we evaluated the hair regrowth activity in response to the upgraded LLLT/GentleWaves® device and Minoxidil.



RESULTS: In the first clinical study, whole-genome analysis of treated scalp biopsies showed downregulation of scalp inflammatory biomarkers, such as AP1/FOSB messenger RNA (mRNA) and mir21, together with the disappearance of CD69 mRNA, specific to scalp-infiltrating T cells of about 50% of the studied volunteers prior to the LLLT/GentleWaves® treatment. In the second clinical study, we observed that LLLT/GentleWaves® was able to boost the hair regrowth activity of a Minoxidil 2% lotion to the extent of the highest concentration (5%) in terms of efficacy, number of responders, and perceived performance.



CONCLUSIONS: Altogether, these observations suggest the potential benefit of LLLT/GentleWaves® as a noninvasive adjunctive technology for skin and scalp conditions, where a mild perifollicular inflammation is involved. Lasers Surg. Med. 2021. Copyright © 2021 Wiley Periodicals LLC.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33334933,

title = {Identifying early pulmonary arterial hypertension biomarkers in systemic sclerosis: machine learning on proteomics from the DETECT cohort},

author = {Yasmina Bauer and Simon de Bernard and Peter Hickey and Karri Ballard and Jeremy Cruz and Peter Cornelisse and Harbajan Chadha-Boreham and Oliver Distler and Daniel Rosenberg and Martin Doelberg and Sebastien Roux and Oliver Nayler and Allan Lawrie},

doi = {10.1183/13993003.02591-2020},

issn = {1399-3003},

year  = {2021},

date = {2021-06-01},

urldate = {2021-06-01},

journal = {Eur Respir J},

volume = {57},

number = {6},

abstract = {Pulmonary arterial hypertension (PAH) is a devastating complication of systemic sclerosis (SSc). Screening for PAH in SSc has increased detection, allowed early treatment for PAH and improved patient outcomes. Blood-based biomarkers that reliably identify SSc patients at risk of PAH, or with early disease, would significantly improve screening, potentially leading to improved survival, and provide novel mechanistic insights into early disease. The main objective of this study was to identify a proteomic biomarker signature that could discriminate SSc patients with and without PAH using a machine learning approach and to validate the findings in an external cohort.Serum samples from patients with SSc and PAH (n=77) and SSc without pulmonary hypertension (non-PH) (n=80) were randomly selected from the clinical DETECT study and underwent proteomic screening using the Myriad RBM Discovery platform consisting of 313 proteins. Samples from an independent validation SSc cohort (PAH n=22 and non-PH n=22) were obtained from the University of Sheffield (Sheffield, UK).Random forest analysis identified a novel panel of eight proteins, comprising collagen IV, endostatin, insulin-like growth factor binding protein (IGFBP)-2, IGFBP-7, matrix metallopeptidase-2, neuropilin-1, N-terminal pro-brain natriuretic peptide and RAGE (receptor for advanced glycation end products), that discriminated PAH from non-PH in SSc patients in the DETECT Discovery Cohort (average area under the receiver operating characteristic curve 0.741, 65.1% sensitivity/69.0% specificity), which was reproduced in the Sheffield Confirmatory Cohort (81.1% accuracy, 77.3% sensitivity/86.5% specificity).This novel eight-protein biomarker panel has the potential to improve early detection of PAH in SSc patients and may provide novel insights into the pathogenesis of PAH in the context of SSc.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32573786,

title = {Dysregulation of microRNA expression in the skin during cutaneous adverse drug reactions},

author = {Eric Pedruzzi and François Chasset and Isabelle Duroux-Richard and David Bocarra and Florence Apparailly and Julien Nourikyan and Mathilde Lumy and Simon de Bernard and Olivia Bonduelle and Laurent Buffat and Behazine Combadière and Angèle Soria},

doi = {10.1111/all.14464},

issn = {1398-9995},

year  = {2020},

date = {2020-12-01},

urldate = {2020-12-01},

journal = {Allergy},

volume = {75},

number = {12},

pages = {3279--3283},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32998444,

title = {When the Search for Stemness Genes Meets the Skin Substitute Bioengineering Field: KLF4 Transcription Factor under the Light},

author = {Nicolas O Fortunel and Michèle T Martin},

doi = {10.3390/cells9102188},

issn = {2073-4409},

year  = {2020},

date = {2020-09-01},

urldate = {2020-09-01},

journal = {Cells},

volume = {9},

number = {10},

abstract = {The transcription factor "Kruppel-like factor 4" (KLF4) is a central player in the field of pluripotent stem cell biology. In particular, it was put under the spotlight as one of the four factors of the cocktail originally described for reprogramming into induced pluripotent stem cells (iPSCs). In contrast, its possible functions in native tissue stem cells remain largely unexplored. We recently published that KLF4 is a regulator of "stemness" in human keratinocytes. We show that reducing the level of expression of this transcription factor by RNA interference or pharmacological repression promotes the ex vivo amplification and regenerative capacity of two types of cells of interest for cutaneous cell therapy: native keratinocyte stem and progenitor cells from adult epidermis, which have been used for more than three decades in skin graft bioengineering, and keratinocytes generated by the lineage-oriented differentiation of embryonic stem cells (ESCs), which have potential for the development of skin bio-bandages. At the mechanistic level, KLF4 repression alters the expression of a large set of genes involved in TGF-β1 and WNT signaling pathways. Major regulators of TGF-β bioavailability and different TGF-β receptors were targeted, notably modulating the ALK1/Smad1/5/9 axis. At a functional level, KLF4 repression produced an antagonist effect on TGFβ1-induced keratinocyte differentiation.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32231305,

title = {Netrin-1 promotes naive pluripotency through Neo1 and Unc5b co-regulation of Wnt and MAPK signalling},

author = {Aurélia Huyghe and Giacomo Furlan and Duygu Ozmadenci and Christina Galonska and Jocelyn Charlton and Xavier Gaume and Noémie Combémorel and Christina Riemenschneider and Nicolas Allègre and Jenny Zhang and Pauline Wajda and Nicolas Rama and Pauline Vieugué and Isabelle Durand and Marie Brevet and Nicolas Gadot and Thomas Imhof and Bradley J Merrill and Manuel Koch and Patrick Mehlen and Claire Chazaud and Alexander Meissner and Fabrice Lavial},

doi = {10.1038/s41556-020-0483-2},

issn = {1476-4679},

year  = {2020},

date = {2020-04-01},

urldate = {2020-04-01},

journal = {Nat Cell Biol},

volume = {22},

number = {4},

pages = {389--400},

abstract = {In mouse embryonic stem cells (mESCs), chemical blockade of Gsk3α/β and Mek1/2 (2i) instructs a self-renewing ground state whose endogenous inducers are unknown. Here we show that the axon guidance cue Netrin-1 promotes naive pluripotency by triggering profound signalling, transcriptomic and epigenetic changes in mESCs. Furthermore, we demonstrate that Netrin-1 can substitute for blockade of Gsk3α/β and Mek1/2 to sustain self-renewal of mESCs in combination with leukaemia inhibitory factor and regulates the formation of the mouse pluripotent blastocyst. Mechanistically, we reveal how Netrin-1 and the balance of its receptors Neo1 and Unc5B co-regulate Wnt and MAPK pathways in both mouse and human ESCs. Netrin-1 induces Fak kinase to inactivate Gsk3α/β and stabilize β-catenin while increasing the phosphatase activity of a Ppp2r2c-containing Pp2a complex to reduce Erk1/2 activity. Collectively, this work identifies Netrin-1 as a regulator of pluripotency and reveals that it mediates different effects in mESCs depending on its receptor dosage, opening perspectives for balancing self-renewal and lineage commitment.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33244316,

title = {Immune Profiles Identification by Vaccinomics After MVA Immunization in Randomized Clinical Study},

author = {Jorge Sanchez and Elena Gonçalves and Anuska Llano and Pedro Gonzáles and María Fernández-Maldonado and Annika Vogt and Angele Soria and Susana Perez and Samandhy Cedeño and Marco Antonio Fernández and Julien Nourikyan and Simon de Bernard and Carmela Ganoza and Eric Pedruzzi and Olivia Bonduelle and Beatriz Mothe and Carmen E Gòmez and Mariano Esteban and Felipe Garcia and Javier R Lama and Christian Brander and Behazine Combadiere},

doi = {10.3389/fimmu.2020.586124},

issn = {1664-3224},

year  = {2020},

date = {2020-01-01},

urldate = {2020-01-01},

journal = {Front Immunol},

volume = {11},

pages = {586124},

abstract = {BACKGROUND: Our previous work has demonstrated the benefits of transcutaneous immunization in targeting Langerhans cells and preferentially inducing CD8 T-cell responses.



METHODS: In this randomized phase Ib clinical trial including 20 HIV uninfected volunteers, we compared the safety and immunogenicity of the MVA recombinant vaccine expressing HIV-B antigen (MVA-B) by transcutaneous and intramuscular routes. We hypothesized that the quality of innate and adaptive immunity differs according to the route of immunization and explored the quality of the vector vaccine-induced immune responses. We also investigated the early blood transcriptome and serum cytokine levels to identify innate events correlated with the strength and quality of adaptive immunity.



RESULTS: We demonstrate that MVA-B vaccine is safe by both routes, but that the quality and intensity of both innate and adaptive immunity differ significantly. Transcutaneous vaccination promoted CD8 responses in the absence of antibodies and slightly affected gene expression, involving mainly genes associated with metabolic pathways. Intramuscular vaccination, on the other hand, drove robust changes in the expression of genes involved in IL-6 and interferon signalling pathways, mainly those associated with humoral responses, and also some levels of CD8 response.



CONCLUSION: Thus, vaccine delivery route perturbs early innate responses that shape the quality of adaptive immunity.



CLINICAL TRIAL REGISTRATION: http://ClinicalTrials.gov, identifier PER-073-13.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31636412,

title = {KLF4 inhibition promotes the expansion of keratinocyte precursors from adult human skin and of embryonic-stem-cell-derived keratinocytes},

author = {Nicolas O Fortunel and Loubna Chadli and Julien Coutier and Gilles Lemaître and Frédéric Auvré and Sophie Domingues and Emmanuelle Bouissou-Cadio and Pierre Vaigot and Sophie Cavallero and Jean-François Deleuze and Paul-Henri Roméo and Michèle T Martin},

doi = {10.1038/s41551-019-0464-6},

issn = {2157-846X},

year  = {2019},

date = {2019-12-01},

urldate = {2019-12-01},

journal = {Nat Biomed Eng},

volume = {3},

number = {12},

pages = {985--997},

abstract = {Expanded autologous skin keratinocytes are currently used in cutaneous cell therapy, and embryonic-stem-cell-derived keratinocytes could become a complementary alternative. Regardless of keratinocyte provenance, for efficient therapy it is necessary to preserve immature keratinocyte precursors during cell expansion and graft processing. Here, we show that stable and transient downregulation of the transcription factor Krüppel-like factor 4 (KLF4) in keratinocyte precursors from adult skin, using anti-KLF4 RNA interference or kenpaullone, promotes keratinocyte immaturity and keratinocyte self-renewal in vitro, and enhances the capacity for epidermal regeneration in mice. Both stable and transient KLF4 downregulation had no impact on the genomic integrity of adult keratinocytes. Moreover, transient KLF4 downregulation in human-embryonic-stem-cell-derived keratinocytes increased the efficiency of skin-orientated differentiation and of keratinocyte immaturity, and was associated with improved generation of epidermis. As a regulator of the cell fate of keratinocyte precursors, KLF4 could be used for promoting the ex vivo expansion and maintenance of functional immature keratinocyte precursors.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid31092846,

title = {Reconstructed Skin Models Revealed Unexpected Differences in Epidermal African and Caucasian Skin},

author = {Sarah Girardeau-Hubert and Céline Deneuville and Hervé Pageon and Kahina Abed and Charlotte Tacheau and Nükhet Cavusoglu and Mark Donovan and Dominique Bernard and Daniel Asselineau},

doi = {10.1038/s41598-019-43128-3},

issn = {2045-2322},

year  = {2019},

date = {2019-05-01},

urldate = {2019-05-01},

journal = {Sci Rep},

volume = {9},

number = {1},

pages = {7456},

abstract = {Clinical observations of both normal and pathological skin have shown that there is a heterogeneity based on the skin origin type. Beside external factors, intrinsic differences in skin cells could be a central element to determine skin types. This study aimed to understand the in vitro behaviour of epidermal cells of African and Caucasian skin types in the context of 3D reconstructed skin. Full-thickness skin models were constructed with site matched human keratinocytes and papillary fibroblasts to investigate potential skin type related differences. We report that reconstructed skin epidermis exhibited remarkable differences regarding stratification and differentiation according to skin types, as demonstrated by histological appearance, gene expression analysed by DNA microarray and quantitative proteomic analysis. Signalling pathways and processes related to terminal differentiation and lipid/ceramide metabolism were up-regulated in epidermis constructed with keratinocytes from Caucasian skin type when compared to that of keratinocytes from African skin type. Specifically, the expression of proteins involved in the processing of filaggrins was found different between skin models. Overall, we show unexpected differences in epidermal morphogenesis and differentiation between keratinocytes of Caucasian and African skin types in in vitro reconstructed skin containing papillary fibroblasts that could explain the differences in ethnic related skin behaviour.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30031067,

title = {Gene profile of zebrafish fin regeneration offers clues to kinetics, organization and biomechanics of basement membrane},

author = {Pauline Nauroy and Alexandre Guiraud and Julien Chlasta and Marilyne Malbouyres and Benjamin Gillet and Sandrine Hughes and Elise Lambert and Florence Ruggiero},

doi = {10.1016/j.matbio.2018.07.005},

issn = {1569-1802},

year  = {2019},

date = {2019-01-01},

urldate = {2019-01-01},

journal = {Matrix Biol},

volume = {75-76},

pages = {82--101},

abstract = {How some animals regenerate missing body parts is not well understood. Taking advantage of the zebrafish caudal fin model, we performed a global unbiased time-course transcriptomic analysis of fin regeneration. Biostatistics analyses identified extracellular matrix (ECM) as the most enriched gene sets. Basement membranes (BMs) are specialized ECM structures that provide tissues with structural cohesion and serve as a major extracellular signaling platform. While the embryonic formation of BM has been extensively investigated, its regeneration in adults remains poorly studied. We therefore focused on BM gene expression kinetics and showed that it recapitulates many aspects of development. As such, the re-expression of the embryonic col14a1a gene indicated that col14a1a is part of the regeneration-specific program. We showed that laminins and col14a1a genes display similar kinetics and that the corresponding proteins are spatially and temporally controlled during regeneration. Analysis of our CRISPR/Cas9-mediated col14a1a knockout fish showed that collagen XIV-A contributes to timely deposition of laminins. As changes in ECM organization can affect tissue mechanical properties, we analyzed the biomechanics of col14a1a regenerative BM using atomic force microscopy (AFM). Our data revealed a thinner BM accompanied by a substantial increase of the stiffness when compared to controls. Further AFM 3D-reconstructions showed that BM is organized as a checkerboard made of alternation of soft and rigid regions that is compromised in mutants leading to a more compact structure. We conclude that collagen XIV-A transiently acts as a molecular spacer responsible for BM structure and biomechanics possibly by helping laminins integration within regenerative BM.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid28435843,

title = {MMP-7 is a predictive biomarker of disease progression in patients with idiopathic pulmonary fibrosis},

author = {Yasmina Bauer and Eric S White and Simon de Bernard and Peter Cornelisse and Isabelle Leconte and Adele Morganti and Sebastien Roux and Oliver Nayler},

doi = {10.1183/23120541.00074-2016},

issn = {2312-0541},

year  = {2017},

date = {2017-01-01},

urldate = {2017-01-01},

journal = {ERJ Open Res},

volume = {3},

number = {1},

abstract = {Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease with poor prognosis, which is characterised by destruction of normal lung architecture and excessive deposition of lung extracellular matrix. The heterogeneity of disease progression in patients with IPF poses significant obstacles to patient care and prevents efficient development of novel therapeutic interventions. Blood biomarkers, reflecting pathobiological processes in the lung, could provide objective evidence of the underlying disease. Longitudinally collected serum samples from the Bosentan Use in Interstitial Lung Disease (BUILD)-3 trial were used to measure four biomarkers (metalloproteinase-7 (MMP-7), Fas death receptor ligand, osteopontin and procollagen type I C-peptide), to assess their potential prognostic capabilities and to follow changes during disease progression in patients with IPF. In baseline BUILD-3 samples, only MMP-7 showed clearly elevated protein levels compared with samples from healthy controls, and further investigations demonstrated that MMP-7 levels also increased over time. Baseline levels of MMP-7 were able to predict patients who had higher risk of worsening and, notably, baseline levels of MMP-7 could predict changes in FVC as early as month 4. MMP-7 shows potential to be a reliable predictor of lung function decline and disease progression.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27924814,

title = {Mature IgM-expressing plasma cells sense antigen and develop competence for cytokine production upon antigenic challenge},

author = {Pascal Blanc and Ludovic Moro-Sibilot and Lucas Barthly and Ferdinand Jagot and Sébastien This and Simon de Bernard and Laurent Buffat and Sébastien Dussurgey and Renaud Colisson and Elias Hobeika and Thierry Fest and Morgan Taillardet and Olivier Thaunat and Antoine Sicard and Paul Mondière and Laurent Genestier and Stephen L Nutt and Thierry Defrance},

doi = {10.1038/ncomms13600},

issn = {2041-1723},

year  = {2016},

date = {2016-12-01},

urldate = {2016-12-01},

journal = {Nat Commun},

volume = {7},

pages = {13600},

abstract = {Dogma holds that plasma cells, as opposed to B cells, cannot bind antigen because they have switched from expression of membrane-bound immunoglobulins (Ig) that constitute the B-cell receptor (BCR) to production of the secreted form of immunoglobulins. Here we compare the phenotypical and functional attributes of plasma cells generated by the T-cell-dependent and T-cell-independent forms of the hapten NP. We show that the nature of the secreted Ig isotype, rather than the chemical structure of the immunizing antigen, defines two functionally distinct populations of plasma cells. Fully mature IgM-expressing plasma cells resident in the bone marrow retain expression of a functional BCR, whereas their IgG counterparts do not. Antigen boost modifies the gene expression profile of IgM plasma cells and initiates a cytokine production program, characterized by upregulation of CCL5 and IL-10. Our results demonstrate that IgM-expressing plasma cells can sense antigen and acquire competence for cytokine production upon antigenic challenge.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26503444,

title = {Terminal NK cell maturation is controlled by concerted actions of T-bet and Zeb2 and is essential for melanoma rejection},

author = {Mary J van Helden and Steven Goossens and Cécile Daussy and Anne-Laure Mathieu and Fabrice Faure and Antoine Marçais and Niels Vandamme and Natalie Farla and Katia Mayol and Sébastien Viel and Sophie Degouve and Emilie Debien and Eve Seuntjens and Andrea Conidi and Julie Chaix and Philippe Mangeot and Simon de Bernard and Laurent Buffat and Jody J Haigh and Danny Huylebroeck and Bart N Lambrecht and Geert Berx and Thierry Walzer},

doi = {10.1084/jem.20150809},

issn = {1540-9538},

year  = {2015},

date = {2015-11-01},

urldate = {2015-11-01},

journal = {J Exp Med},

volume = {212},

number = {12},

pages = {2015--2025},

abstract = {Natural killer (NK) cell maturation is a tightly controlled process that endows NK cells with functional competence and the capacity to recognize target cells. Here, we found that the transcription factor (TF) Zeb2 was the most highly induced TF during NK cell maturation. Zeb2 is known to control epithelial to mesenchymal transition, but its role in immune cells is mostly undefined. Targeted deletion of Zeb2 resulted in impaired NK cell maturation, survival, and exit from the bone marrow. NK cell function was preserved, but mice lacking Zeb2 in NK cells were more susceptible to B16 melanoma lung metastases. Reciprocally, ectopic expression of Zeb2 resulted in a higher frequency of mature NK cells in all organs. Moreover, the immature phenotype of Zeb2(-/-) NK cells closely resembled that of Tbx21(-/-) NK cells. This was caused by both a dependence of Zeb2 expression on T-bet and a probable cooperation of these factors in gene regulation. Transgenic expression of Zeb2 in Tbx21(-/-) NK cells partially restored a normal maturation, establishing that timely induction of Zeb2 by T-bet is an essential event during NK cell differentiation. Finally, this novel transcriptional cascade could also operate in human as T-bet and Zeb2 are similarly regulated in mouse and human NK cells.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25029475,

title = {A novel genomic signature with translational significance for human idiopathic pulmonary fibrosis},

author = {Yasmina Bauer and John Tedrow and Simon de Bernard and Magdalena Birker-Robaczewska and Kevin F Gibson and Brenda Juan Guardela and Patrick Hess and Axel Klenk and Kathleen O Lindell and Sylvie Poirey and Bérengère Renault and Markus Rey and Edgar Weber and Oliver Nayler and Naftali Kaminski},

doi = {10.1165/rcmb.2013-0310OC},

issn = {1535-4989},

year  = {2015},

date = {2015-02-01},

urldate = {2015-02-01},

journal = {Am J Respir Cell Mol Biol},

volume = {52},

number = {2},

pages = {217--231},

abstract = {The bleomycin-induced rodent lung fibrosis model is commonly used to study mechanisms of lung fibrosis and to test potential therapeutic interventions, despite the well recognized dissimilarities to human idiopathic pulmonary fibrosis (IPF). Therefore, in this study, we sought to identify genomic commonalities between the gene expression profiles from 100 IPF lungs and 108 control lungs that were obtained from the Lung Tissue Research Consortium, and rat lungs harvested at Days 3, 7, 14, 21, 28, 42, and 56 after bleomycin instillation. Surprisingly, the highest gene expression similarity between bleomycin-treated rat and IPF lungs was observed at Day 7. At this point of maximal rat-human commonality, we identified a novel set of 12 disease-relevant translational gene markers (C6, CTHRC1, CTSE, FHL2, GAL, GREM1, LCN2, MMP7, NELL1, PCSK1, PLA2G2A, and SLC2A5) that was able to separate almost all patients with IPF from control subjects in our cohort and in two additional IPF/control cohorts (GSE10667 and GSE24206). Furthermore, in combination with diffusing capacity of carbon monoxide measurements, four members of the translational gene marker set contributed to stratify patients with IPF according to disease severity. Significantly, pirfenidone attenuated the expression change of one (CTHRC1) translational gene marker in the bleomycin-induced lung fibrosis model, in transforming growth factor-β1-treated primary human lung fibroblasts and transforming growth factor-β1-treated human epithelial A549 cells. Our results suggest that a strategy focused on rodent model-human disease commonalities may identify genes that could be used to predict the pharmacological impact of therapeutic interventions, and thus facilitate the development of novel treatments for this devastating lung disease.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25209580,

title = {Dramatic response of a BRAF V600E-mutated primary CNS histiocytic sarcoma to vemurafenib},

author = {Ahmed Idbaih and Karima Mokhtari and Jean-François Emile and Damien Galanaud and Hayat Belaid and Simon de Bernard and Neila Benameur and Vlad-Ciprian Barlog and Dimitri Psimaras and Jean Donadieu and Catherine Carpentier and Nadine Martin-Duverneuil and Julien Haroche and Loic Feuvret and Noel Zahr and Jean-Yves Delattre and Khê Hoang-Xuan},

doi = {10.1212/WNL.0000000000000880},

issn = {1526-632X},

year  = {2014},

date = {2014-10-01},

urldate = {2014-10-01},

journal = {Neurology},

volume = {83},

number = {16},

pages = {1478--1480},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24516120,

title = {T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow},

author = {Cécile Daussy and Fabrice Faure and Katia Mayol and Sébastien Viel and Georg Gasteiger and Emily Charrier and Jacques Bienvenu and Thomas Henry and Emilie Debien and Uzma A Hasan and Jacqueline Marvel and Keigyou Yoh and Satoru Takahashi and Immo Prinz and Simon de Bernard and Laurent Buffat and Thierry Walzer},

doi = {10.1084/jem.20131560},

issn = {1540-9538},

year  = {2014},

date = {2014-03-01},

urldate = {2014-03-01},

journal = {J Exp Med},

volume = {211},

number = {3},

pages = {563--577},

abstract = {Trail(+)DX5(-)Eomes(-) natural killer (NK) cells arise in the mouse fetal liver and persist in the adult liver. Their relationships with Trail(-)DX5(+) NK cells remain controversial. We generated a novel Eomes-GFP reporter murine model to address this question. We found that Eomes(-) NK cells are not precursors of classical Eomes(+) NK cells but rather constitute a distinct lineage of innate lymphoid cells. Eomes(-) NK cells are strictly dependent on both T-bet and IL-15, similarly to NKT cells. We observed that, in the liver, expression of T-bet in progenitors represses Eomes expression and the development of Eomes(+) NK cells. Reciprocally, the bone marrow (BM) microenvironment restricts T-bet expression in developing NK cells. Ectopic expression of T-bet forces the development of Eomes(-) NK cells, demonstrating that repression of T-bet is essential for the development of Eomes(+) NK cells. Gene profile analyses show that Eomes(-) NK cells share part of their transcriptional program with NKT cells, including genes involved in liver homing and NK cell receptors. Moreover, Eomes(-) NK cells produce a broad range of cytokines, including IL-2 and TNF in vitro and in vivo, during immune responses against vaccinia virus. Thus, mutually exclusive expression of T-bet and Eomes drives the development of different NK cell lineages with complementary functions.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24422634,

title = {Retinoic acid receptor subtype-specific transcriptotypes in the early zebrafish embryo},

author = {Eric Samarut and Cyril Gaudin and Sandrine Hughes and Benjamin Gillet and Simon de Bernard and Pierre-Emmanuel Jouve and Laurent Buffat and Alexis Allot and Odile Lecompte and Liubov Berekelya and Cécile Rochette-Egly and Vincent Laudet},

doi = {10.1210/me.2013-1358},

issn = {1944-9917},

year  = {2014},

date = {2014-02-01},

urldate = {2014-02-01},

journal = {Mol Endocrinol},

volume = {28},

number = {2},

pages = {260--272},

abstract = {Retinoic acid (RA) controls many aspects of embryonic development by binding to specific receptors (retinoic acid receptors [RARs]) that regulate complex transcriptional networks. Three different RAR subtypes are present in vertebrates and play both common and specific roles in transducing RA signaling. Specific activities of each receptor subtype can be correlated with its exclusive expression pattern, whereas shared activities between different subtypes are generally assimilated to functional redundancy. However, the question remains whether some subtype-specific activity still exists in regions or organs coexpressing multiple RAR subtypes. We tackled this issue at the transcriptional level using early zebrafish embryo as a model. Using morpholino knockdown, we specifically invalidated the zebrafish endogenous RAR subtypes in an in vivo context. After building up a list of RA-responsive genes in the zebrafish gastrula through a whole-transcriptome analysis, we compared this panel of genes with those that still respond to RA in embryos lacking one or another RAR subtype. Our work reveals that RAR subtypes do not have fully redundant functions at the transcriptional level but can transduce RA signal in a subtype-specific fashion. As a result, we define RAR subtype-specific transcriptotypes that correspond to repertoires of genes activated by different RAR subtypes. Finally, we found genes of the RA pathway (cyp26a1, raraa) the regulation of which by RA is highly robust and can even resist the knockdown of all RARs. This suggests that RA-responsive genes are differentially sensitive to alterations in the RA pathway and, in particular, cyp26a1 and raraa are under a high pressure to maintain signaling integrity.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid25566510,

title = {Granulomatous response to Coxiella burnetii, the agent of Q fever: the lessons from gene expression analysis},

author = {Delphine Faugaret and Amira Ben Amara and Julie Alingrin and Aurélie Daumas and Amélie Delaby and Catherine Lépolard and Didier Raoult and Julien Textoris and Jean-Louis Mège},

doi = {10.3389/fcimb.2014.00172},

issn = {2235-2988},

year  = {2014},

date = {2014-01-01},

urldate = {2014-01-01},

journal = {Front Cell Infect Microbiol},

volume = {4},

pages = {172},

abstract = {The formation of granulomas is associated with the resolution of Q fever, a zoonosis due to Coxiella burnetii; however the molecular mechanisms of granuloma formation remain poorly understood. We generated human granulomas with peripheral blood mononuclear cells (PBMCs) and beads coated with C. burnetii, using BCG extracts as controls. A microarray analysis showed dramatic changes in gene expression in granuloma cells of which more than 50% were commonly modulated genes in response to C. burnetii and BCG. They included M1-related genes and genes related to chemotaxis. The inhibition of the chemokines, CCL2 and CCL5, directly interfered with granuloma formation. C. burnetii granulomas also expressed a specific transcriptional profile that was essentially enriched in genes associated with type I interferon response. Our results showed that granuloma formation is associated with a core of transcriptional response based on inflammatory genes. The specific granulomatous response to C. burnetii is characterized by the activation of type 1 interferon pathway.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23840433,

title = {Differentially expressed androgen-regulated genes in androgen-sensitive tissues reveal potential biomarkers of early prostate cancer},

author = {Dogus Murat Altintas and Nathalie Allioli and Myriam Decaussin and Simon de Bernard and Alain Ruffion and Jacques Samarut and Virginie Vlaeminck-Guillem},

doi = {10.1371/journal.pone.0066278},

issn = {1932-6203},

year  = {2013},

date = {2013-01-01},

urldate = {2013-01-01},

journal = {PLoS One},

volume = {8},

number = {6},

pages = {e66278},

abstract = {BACKGROUND: Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer.



METHODS: ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens) using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1).



RESULTS AND DISCUSSION: By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91) and DLX1 (0.94).



CONCLUSIONS: We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could be complementary to known genes overexpressed in PCa and included along with them in multiplex diagnostic tools.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24039440,

title = {A new Vitreoscilla filiformis extract grown on spa water-enriched medium activates endogenous cutaneous antioxidant and antimicrobial defenses through a potential Toll-like receptor 2/protein kinase C, zeta transduction pathway},

author = {Yann F Mahe and Marie-Jesus Perez and Charlotte Tacheau and Chantal Fanchon and Richard Martin and Françoise Rousset and Sophie Seite},

doi = {10.2147/CCID.S47324},

issn = {1178-7015},

year  = {2013},

date = {2013-01-01},

urldate = {2013-01-01},

journal = {Clin Cosmet Investig Dermatol},

volume = {6},

pages = {191--196},

abstract = {Vitreoscilla filiformis (VF) biomass (VFB) has been widely used in cosmetic preparations and shown to modulate the major inducible free-radical scavenger mitochondrial superoxide dismutase in skin cells. By adding La Roche-Posay (LRP) thermal spring water to the VF culture medium, we obtained a biomass (LRP-VFB) with a similar mitochondrial superoxide dismutase activation capacity to VF. Also, the new biomass more powerfully stimulated mRNA expression and antimicrobial peptides in reconstructed epidermis. Interestingly, a predictive computer model that analyzed transducing events within skin epidermal cells suggested that this protective activity may involve the Toll-like receptor 2/protein kinase C, zeta transduction pathway. Protein kinase C, zeta inhibition was effectively shown to abolish VFB-induced gene stimulation and confirmed this hypothesis. This thus opens new avenues for investigation into the improvement of skin homeostatic defense in relation to the control of its physiological microbiota and innate immunity.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23071531,

title = {SNP array analysis reveals novel genomic abnormalities including copy neutral loss of heterozygosity in anaplastic oligodendrogliomas},

author = {Ahmed Idbaih and François Ducray and Caroline Dehais and Célia Courdy and Catherine Carpentier and Simon de Bernard and Emmanuelle Uro-Coste and Karima Mokhtari and Anne Jouvet and Jérôme Honnorat and Olivier Chinot and Carole Ramirez and Patrick Beauchesne and Alexandra Benouaich-Amiel and Joël Godard and Sandrine Eimer and Fabrice Parker and Emmanuelle Lechapt-Zalcman and Philippe Colin and Delphine Loussouarn and Thierry Faillot and Phong Dam-Hieu and Selma Elouadhani-Hamdi and Luc Bauchet and Olivier Langlois and Caroline Le Guerinel and Denys Fontaine and Elodie Vauleon and Philippe Menei and Marie Janette Motsuo Fotso and Christine Desenclos and Pierre Verrelle and François Ghiringhelli and Georges Noel and François Labrousse and Antoine Carpentier and Frédéric Dhermain and Jean-Yves Delattre and Dominique Figarella-Branger},

doi = {10.1371/journal.pone.0045950},

issn = {1932-6203},

year  = {2012},

date = {2012-01-01},

urldate = {2012-01-01},

journal = {PLoS One},

volume = {7},

number = {10},

pages = {e45950},

abstract = {Anaplastic oligodendrogliomas (AOD) are rare glial tumors in adults with relative homogeneous clinical, radiological and histological features at the time of diagnosis but dramatically various clinical courses. Studies have identified several molecular abnormalities with clinical or biological relevance to AOD (e.g. t(1;19)(q10;p10), IDH1, IDH2, CIC and FUBP1 mutations).To better characterize the clinical and biological behavior of this tumor type, the creation of a national multicentric network, named "Prise en charge des OLigodendrogliomes Anaplasiques (POLA)," has been supported by the Institut National du Cancer (InCA). Newly diagnosed and centrally validated AOD patients and their related biological material (tumor and blood samples) were prospectively included in the POLA clinical database and tissue bank, respectively.At the molecular level, we have conducted a high-resolution single nucleotide polymorphism array analysis, which included 83 patients. Despite a careful central pathological review, AOD have been found to exhibit heterogeneous genomic features. A total of 82% of the tumors exhibited a 1p/19q-co-deletion, while 18% harbor a distinct chromosome pattern. Novel focal abnormalities, including homozygously deleted, amplified and disrupted regions, have been identified. Recurring copy neutral losses of heterozygosity (CNLOH) inducing the modulation of gene expression have also been discovered. CNLOH in the CDKN2A locus was associated with protein silencing in 1/3 of the cases. In addition, FUBP1 homozygous deletion was detected in one case suggesting a putative tumor suppressor role of FUBP1 in AOD.Our study showed that the genomic and pathological analyses of AOD are synergistic in detecting relevant clinical and biological subgroups of AOD.},

keywords = {omics},

pubstate = {published},

tppubtype = {article}

}