UCAGenomiX related publications

Du to our strong expertise in "omics" experiments and in microRNAs topics we decided to separate into 3 categories the related publications into which the Functional genomics Platform of Nice-Sophia-Antipolis is involved :
  1. Expression studies (DNA microarrays and high-throughput sequencing experiments)
  2. MicroRNA studies
  3. Miscellaneous

Chevalier Benoit

 chevalier@ipmc.cnrs.fr
 04 93 95 77 90
 660 route des lucioles 06560 Valbonne - Sophia-Antipolis

9 publications found

1. The "one airway, one disease" concept in light of Th2 inflammation.
Eur Respir J. 2018 Sep 6. pii: 1800437. doi: 10.1183/13993003.00437-2018.
Giovannini-Chami L, Paquet A, Sanfiorenzo C, Pons N, Cazareth J, Magnone V, Lebrigand K, Chevalier B, Vallauri A, Julia V, Marquette CH, Marcet B, Leroy S, Barbry P
Université Côte d'Azur, Hôpitaux pédiatriques de Nice CHU-Lenval, Pediatric Pulmonology and Allergology Department, Nice, France. Université Côte d'Azur, CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, Sophia Antipolis, France. Université Côte d'Azur, CHU de Nice, FHU Oncoage, Pulmonology Department, Nice, France.

In line with the pathophysiological continuum described between nose and bronchus in allergic respiratory diseases, we assessed whether nasal epithelium could mirror the Th2 status of bronchial epithelium.Nasal and bronchial cells were collected by brushings from patients with allergic rhinitis and asthma (AR, n=12), isolated allergic rhinitis (R, n=14) and healthy controls (C, n=13). Cellular composition was assessed by flow cytometry. Gene expression was analysed by RNA sequencing. Th2, Th17 and interferon signatures were derived from the literature.Infiltration by polymorphonuclear neutrophils in nose excluded 30% of the initial cohort. All bronchial samples from AR group were Th2-high. Nasal samples gene expression profile from the AR group correctly predicted the paired bronchial sample Th2 status in 71% of cases. Nevertheless, nasal cells did not appear as a reliable surrogate of the Th2 response, in particular due to a more robust influence of the interferon response in 14/26 nasal samples. Th2 scores correlated with mast cells counts (p<0.001) and numbers of sensitizations (p=0.006 and 0.002), while Th17 scores correlated with PMN counts (p<0.014).The large variability in nasal cell composition and type of inflammation restricts its use as a surrogate for assessing bronchial Th2 inflammation in AR patients.
Pubmed link : 30190271

2. Characterizing isomiR variants within the microRNA-34/449 family
FEBS Lett. 2017 Mar;591(5):693-705. doi: 10.1002/1873-3468.12595. Epub 2017 Feb 28
Mercey O, Popa A, Cavard A, Paquet A, Chevalier B, Pons N, Magnone V, Zangari J, Brest P, Zaragosi LE, Ponzio G, Lebrigand K, Barbry P, Marcet B
CNRS, IPMC, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France. CNRS, INSERM, IRCAN, FHU-OncoAge, Université Côte d'Azur, Sophia-Antipolis, Valbonne, France.

miR-34/449 microRNAs are conserved regulators of multiciliated cell differentiation. Here, we evidence and characterize expression of two isomiR variant sequences from the miR-34/449 family in human airway epithelial cells. These isomiRs differ from their canonical counterparts miR-34b and miR-449c by one supplemental uridine at their 5'-end, leading to a one-base shift in their seed region. Overexpression of canonical miR-34/449 or 5'-isomiR-34/449 induces distinct gene expression profiles and biological effects. However, some target transcripts and functional activities are shared by both canonical microRNAs and isomiRs. Indeed, both repress important targets that result in cell cycle blockage and Notch pathway inhibition. Our findings suggest that 5'-isomiR-34/449 may represent additional mechanisms by which miR-34/449 family finely controls several pathways to drive multiciliogenesis.
Pubmed link : 28192603

3. miR-34/449 control apical actin network formation during multiciliogenesis through small GTPase pathways.
Nat Commun. 2015 Sep 18;6:8386. doi: 10.1038/ncomms9386.
Chevalier B, Adamiok A, Mercey O, Revinski DR, Zaragosi LE, Pasini A, Kodjabachian L, Barbry P, Marcet B
1CNRS, Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR-7275, 660 route des Lucioles, 06560 Sophia-Antipolis, France. 2University of Nice-Sophia-Antipolis (UNS), Institut de Pharmacologie Moléculaire et Cellulaire, 660 route des Lucioles, Valbonne, 06560 Sophia-Antipolis, France. 3Aix-Marseille Université, CNRS, UMR7288, Institut de Biologie du Développement de Marseille (IBDM), 13288 Marseille, France.

Vertebrate multiciliated cells (MCCs) contribute to fluid propulsion in several biological processes. We previously showed that microRNAs of the miR-34/449 family trigger MCC differentiation by repressing cell cycle genes and the Notch pathway. Here, using human and Xenopus MCCs, we show that beyond this initial step, miR-34/449 later promote the assembly of an apical actin network, required for proper basal bodies anchoring. Identification of miR-34/449 targets related to small GTPase pathways led us to characterize R-Ras as a key regulator of this process. Protection of RRAS messenger RNA against miR-34/449 binding impairs actin cap formation and multiciliogenesis, despite a still active RhoA. We propose that miR-34/449 also promote relocalization of the actin binding protein Filamin-A, a known RRAS interactor, near basal bodies in MCCs. Our study illustrates the intricate role played by miR-34/449 in coordinating several steps of a complex differentiation programme by regulating distinct signalling pathways.
Pubmed link : 26381333

4. BMP signalling controls the construction of vertebrate mucociliary epithelia.
Development. 2015 Jul 1;142(13):2352-63. doi: 10.1242/dev.118679. Epub 2015 Jun 19.
Cibois M, Luxardi G, Chevalier B, Thomé V, Mercey O, Zaragosi LE, Barbry P, Pasini A, Marcet B, Kodjabachian L
1Aix-Marseille Université, CNRS, IBDM, Marseille 13288, France. 2CNRS, IPMC, Sophia-Antipolis 06560, France. 3CNRS, IPMC, Sophia-Antipolis 06560, France University of Nice Sophia Antipolis (UNS), IPMC, Sophia-Antipolis 06560, France. 4Aix-Marseille Université, CNRS, IBDM, Marseille 13288, France laurent.kodjabachian@univ-amu.fr.

Despite the importance of mucociliary epithelia in animal physiology, the mechanisms controlling their establishment are poorly understood. Using the developing Xenopus epidermis and regenerating human upper airways, we reveal the importance of BMP signalling for the construction of vertebrate mucociliary epithelia. In Xenopus, attenuation of BMP activity is necessary for the specification of multiciliated cells (MCCs), ionocytes and small secretory cells (SSCs). Conversely, BMP activity is required for the proper differentiation of goblet cells. Our data suggest that the BMP and Notch pathways interact to control fate choices in the developing epidermis. Unexpectedly, BMP activity is also necessary for the insertion of MCCs, ionocytes and SSCs into the surface epithelium. In human, BMP inhibition also strongly stimulates the formation of MCCs in normal and pathological (cystic fibrosis) airway samples, whereas BMP overactivation has the opposite effect. This work identifies the BMP pathway as a key regulator of vertebrate mucociliary epithelium differentiation and morphogenesis.
Pubmed link : 26092849

5. Distinct epithelial gene expression phenotypes in childhood respiratory allergy.
Eur Respir J. 2012 May;39(5):1197-205. Epub 2011 Oct 17.
Giovannini-Chami L, Marcet B, Moreilhon C, Chevalier B, Illie MI, Lebrigand K, Robbe-Sermesant K, Bourrier T, Michiels JF, Mari B, Crénesse D, Hofman P, de Blic J, Castillo L, Albertini M, Barbry P
CNRS and University of Nice Sophia Antipolis, Institut de Pharmacologie Moléculaire et Cellulaire, UMR 7275, Sophia Antipolis, 06560 Sophia Antipolis, France.

Epithelial cell contribution to the natural history of childhood allergic respiratory disease remains poorly understood. Our aims were to identify epithelial pathways that are dysregulated in different phenotypes of respiratory allergy. We established gene expression signatures of nasal brushings from children with dust mite-allergic rhinitis, associated or not associated with controlled or uncontrolled asthma. Supervised learning and unsupervised clustering were used to predict the different subgroups of patients and define altered signalling pathways. These profiles were compared with those of primary cultures of human nasal epithelial cells stimulated with either interleukin (IL)-4, IL-13, interferon (IFN)-α, IFN-β or IFN-γ, or during in vitro differentiation. A supervised method discriminated children with allergic rhinitis from healthy controls (prediction accuracy 91%), based on 61 transcripts, including 21 T-helper cell (Th) type 2-responsive genes. This method was then applied to predict children with controlled or uncontrolled asthma (prediction accuracy 75%), based on 41 transcripts: nine of them, which were down-regulated in uncontrolled asthma, are directly linked to IFN. This group also included GSDML, which is genetically associated with asthma. Our data revealed a Th2-driven epithelial phenotype common to all children with dust mite allergic rhinitis. It highlights the influence of epithelially expressed molecules on the control of asthma, in association with atopy and impaired viral response.
Pubmed link : 22005912

6. MicroRNA-based silencing of Delta/Notch signaling promotes multiple cilia formation.
Cell Cycle. 2011 Sep 1;10(17):2858-64. Epub 2011 Sep 1.
Marcet B, Chevalier B, Coraux C, Kodjabachian L, Barbry P
Centre National de la Recherche Scientifique (CNRS), Institut de Pharmacologie Moléculaire et Cellulaire, UMR-6097, Sophia-Antipolis, France. marcet@ipmc.cnrs.fr

Multiciliated cells lining the surface of some vertebrate epithelia are essential for various physiological processes, such as airway cleansing. Their apical surface is constituted by hundreds of motile cilia, which beat in a coordinated manner to generate directional fluid flow. We recently reported the identification of microRNAs of the miR-449 family as evolutionary conserved key regulators of vertebrate multiciliogenesis. This novel function of miR-449 was established using in vivo and in vitro antisense approaches in two distinct experimental models. miR-449 strongly accumulated in multiciliated cells in human airway epithelium and Xenopus laevis embryonic epidermis, where it triggered centriole multiplication and multiciliogenesis by directly repressing the Delta/Notch pathway. Our data complement previous reports that showed the blocking action of miR-449 on the cell cycle, and unraveled a novel conserved mechanism whereby Notch signaling must undergo microRNA-mediated inhibition to permit differentiation of ciliated cell progenitors. We review here several important questions regarding the links between microRNAs and the Notch pathway in the control of cell fate.
Pubmed link : 21857154

7. MicroRNA control biosynthesis of motile cilia in vertebrates.
Med Sci (Paris). 2011 Jun-Jul;27(6-7):671-3. Epub 2011 Jul 1.
Chevalier B, Kodjabachian L, Coraux C, Barbry P, Marcet B
IPMC

Article in French
Pubmed link : 21718654

8. Control of vertebrate multiciliogenesis by miR-449 through direct repression of the Delta/Notch pathway.
Nat Cell Biol. 2011 Jun;13(6):693-9. Epub 2011 May 22.
Marcet B, Chevalier B, Luxardi G, Coraux C, Zaragosi LE, Cibois M, Robbe-Sermesant K, Jolly T, Cardinaud B, Moreilhon C, Giovannini-Chami L, Nawrocki-Raby B, Birembaut P, Waldmann R, Kodjabachian L, Barbry P
CNRS, Institut de Pharmacologie Moléculaire et Cellulaire, F06560 Sophia Antipolis, France.

Multiciliated cells lining the surface of some vertebrate epithelia are essential for various physiological processes, such as airway cleansing. However, the mechanisms governing motile cilia biosynthesis remain poorly elucidated. We identify miR-449 microRNAs as evolutionarily conserved key regulators of vertebrate multiciliogenesis. In human airway epithelium and Xenopus laevis embryonic epidermis, miR-449 microRNAs strongly accumulated in multiciliated cells. In both models, we show that miR-449 microRNAs promote centriole multiplication and multiciliogenesis by directly repressing the Delta/Notch pathway. We established Notch1 and its ligand Delta-like 1(DLL1) as miR-449 bona fide targets. Human DLL1 and NOTCH1 protein levels were lower in multiciliated cells than in surrounding cells, decreased after miR-449 overexpression and increased after miR-449 inhibition. In frog, miR-449 silencing led to increased Dll1 expression. Consistently, overexpression of Dll1 mRNA lacking miR-449 target sites repressed multiciliogenesis, whereas both Dll1 and Notch1 knockdown rescued multiciliogenesis in miR-449-deficient cells. Antisense-mediated protection of miR-449-binding sites of endogenous human Notch1 or frog Dll1 strongly repressed multiciliogenesis. Our results unravel a conserved mechanism whereby Notch signalling must undergo miR-449-mediated inhibition to permit differentiation of ciliated cell progenitors.
Pubmed link : 21602795

9. Identification of keratinocyte growth factor as a target of microRNA-155 in lung fibroblasts: implication in epithelial-mesenchymal interactions.
PLoS One. 2009 Aug 24;4(8):e6718.
Pottier N, Maurin T, Chevalier B, Puissegur MP, Lebrigand K, Robbe-Sermesant K, Bertero T, Lino Cardenas CL, Courcot E, Rios G, Fourre S, Lo-Guidice JM, Marcet B, Cardinaud B, Barbry P, Mari B
CNRS, Institut de Pharmacologie Moleculaire et Cellulaire, UMR6097, Sophia Antipolis, France.

BACKGROUND: Epithelial-mesenchymal interactions are critical in regulating many aspects of vertebrate embryo development, and for the maintenance of homeostatic equilibrium in adult tissues. The interactions between epithelium and mesenchyme are believed to be mediated by paracrine signals such as cytokines and extracellular matrix components secreted from fibroblasts that affect adjacent epithelia. In this study, we sought to identify the repertoire of microRNAs (miRNAs) in normal lung human fibroblasts and their potential regulation by the cytokines TNF-alpha, IL-1beta and TGF-beta. METHODOLOGY/PRINCIPAL FINDINGS: MiR-155 was significantly induced by inflammatory cytokines TNF-alpha and IL-1beta while it was down-regulated by TGF-beta. Ectopic expression of miR-155 in human fibroblasts induced modulation of a large set of genes related to "cell to cell signalling", "cell morphology" and "cellular movement". This was consistent with an induction of caspase-3 activity and with an increase in cell migration in fibroblasts tranfected with miR-155. Using different miRNA bioinformatic target prediction tools, we found a specific enrichment for miR-155 predicted targets among the population of down-regulated transcripts. Among fibroblast-selective targets, one interesting hit was keratinocyte growth factor (KGF, FGF-7), a member of the fibroblast growth factor (FGF) family, which owns two potential binding sites for miR-155 in its 3'-UTR. Luciferase assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Site-directed mutagenesis revealed that only one out of the 2 potential sites was truly functional. Functional in vitro assays experimentally validated that miR-155 can efficiently target KGF 3'-UTR. Furthermore, in vivo experiments using a mouse model of lung fibrosis showed that miR-155 expression level was correlated with the degree of lung fibrosis. CONCLUSIONS/SIGNIFICANCE: Our results strongly suggest a physiological function of miR-155 in lung fibroblasts. Altogether, this study implicates this miRNA in the regulation by mesenchymal cells of surrounding lung epithelium, making it a potential key player during tissue injury.
Pubmed link : 19701459