title: Small RNA sequencing reveals miR-642a-3p as a novel adipocyte-specific microRNA and miR-30 as a key regulator of human adipogenesis.
abstract: BACKGROUND
  In severe obesity, as well as in normal development, the growth of adipose tissue is the result of an increase in adipocyte size and numbers, which is underlain by the stimulation of adipogenic differentiation of precursor cells. A better knowledge of the pathways that regulate adipogenesis is therefore essential for an improved understanding of adipose tissue expansion. As microRNAs (miRNAs) have a critical role in many differentiation processes, our study aimed to identify the role of miRNA-mediated gene silencing in the regulation of adipogenic differentiation.
  
  
  RESULTS
  We used deep sequencing to identify small RNAs that are differentially expressed during adipogenesis of adipose tissue-derived stem cells. This approach revealed the un-annotated miR-642a-3p as a highly adipocyte-specific miRNA. We then focused our study on the miR-30 family, which was also up-regulated during adipogenic differentiation and for which the role in adipogenesis had not yet been elucidated. Inhibition of the miR-30 family blocked adipogenesis, whilst over-expression of miR-30a and miR-30d stimulated this process. We additionally showed that both miR-30a and miR-30d target the transcription factor RUNX2, and stimulate adipogenesis via the modulation of this major regulator of osteogenesis.
  
  
  CONCLUSIONS
  Overall, our data suggest that the miR-30 family plays a central role in adipocyte development. Moreover, as adipose tissue-derived stem cells can differentiate into either adipocytes or osteoblasts, the down-regulation of the osteogenesis regulator RUNX2 represents a plausible mechanism by which miR-30 miRNAs may contribute to adipogenic differentiation of adipose tissue-derived stem cells.
authors.affiliation: Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, UMR-6097, 660 Route des Lucioles, Valbonne Sophia-Antipolis 06560, France.
authors.forename: Laure-Emmanuelle
authors.initials: LE
authors.lastname: Zaragosi
authors.forename: Brigitte
authors.initials: B
authors.lastname: Wdziekonski
authors.forename: Kevin Le
authors.initials: KL
authors.lastname: Brigand
authors.forename: Phi
authors.initials: P
authors.lastname: Villageois
authors.forename: Bernard
authors.initials: B
authors.lastname: Mari
authors.forename: Rainer
authors.initials: R
authors.lastname: Waldmann
authors.forename: Christian
authors.initials: C
authors.lastname: Dani
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbry
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000037:antagonists & inhibitors / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D035683:MicroRNAs / Q000737:chemistry / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics; D017423:Sequence Analysis, RNA; D015854:Up-Regulation / Q000235:genetics
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C546086:MIRN30b microRNA, human; C571933:MIRN642 microRNA, human; D035683:MicroRNAs