title: Basal autophagy decreased during the differentiation of human adult mesenchymal stem cells.
abstract: Autophagy plays an important role in homeostasis, development, and disease, functioning both as a survival and cell death pathway. However, despite its importance in cell physiology, there is little information about the role of autophagy in stem cells and, in particular, on its implication in their survival and/or cell death. We describe here that in vitro, human mesenchymal stem cells (hMSCs) exhibited a high level of constitutive autophagy. Inhibitors of autophagy such as Bafilomycin A1 (Baf-A1) inhibited the proteolytic degradation associated with autophagy in these cells. In addition, we show that a knockdown in the expression of Bcl-xL is accompanied by a loss of autophagic proteolytic ability. Indeed, Bcl-xL seems to exert a tight control on autophagy regulation, since its reintroduction by a protein construct PTD-Bcl-xL resulted in the reacquisition of autophagy. We show that the suppression of autophagy through the knockdown of Bcl-xL influenced hMSC survival and differentiation. This study expands our knowledge on the control exerted by Bcl-xL on autophagy and illustrates the important role of autophagy in the maintenance and differentiation of adult hMSCs.
authors.affiliation: UMR INSERM 892-CNRS 6299, Centre de Recherche en Cance´rologie Nantes-Angers, Nantes, France.
authors.forename: Lisa
authors.initials: L
authors.lastname: Oliver
authors.forename: Erika
authors.initials: E
authors.lastname: Hue
authors.forename: Muriel
authors.initials: M
authors.lastname: Priault
authors.forename: François M
authors.initials: FM
authors.lastname: Vallette
mesh_terms: D053687:Adult Stem Cells / Q000502:physiology*; D001343:Autophagy; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D059748:Proteolysis; D059008:Time-Lapse Imaging; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: C494811:BCL2L1 protein, human; C502070:MAP1LC3B protein, human; D008869:Microtubule-Associated Proteins; D051020:bcl-X Protein