title: Differentiation-related response to DNA breaks in human mesenchymal stem cells.
abstract: We have recently shown that the in vitro differentiation of human mesenchymal stem cells (hMSCs) was accompanied by an increased sensitivity toward apoptosis; however, the mechanism responsible for this shift is not known. Here, we show that the repair of DNA double-strand breaks (DSBs) was more rapid in undifferentiated hMSCs than in differentiated osteoblasts by quantification of the disappearance of γ-H2AX foci in the nuclei after γ-irradiation-induced DNA damage. In addition, there was a marked and prolonged increase in the level of nuclear Ku70 and an increased phosphorylation of DNA-PKcs. This was accompanied by an augmentation in the phosphorylation of ATM in hMSCs post-irradiation suggesting the nonhomologous end joining repair mechanism. However, when hMSCs were induced to differentiate along the osteogenic or adipogenic pathways; irradiation of these cells caused an expeditious and robust cell death, which was primarily apoptotic. This was in sharp contrast to undifferentiated hMSCs, which were highly resistant to irradiation and/or temozolomide-induced DSBs. In addition, we observed a 95% recovery from DSB in these cells. Our results suggest that apoptosis and DNA repair are major safeguard mechanisms in the control of hMSCs differentiation after DNA damage.
authors: CRCNA-INSERM UMR 892-CNRS UMR 6299, Nantes, France.
authors: Lisa
authors: L
authors: Oliver
authors: Erika
authors: E
authors: Hue
authors: Quentin
authors: Q
authors: Séry
authors: Audrey
authors: A
authors: Lafargue
authors: Claire
authors: C
authors: Pecqueur
authors: François
authors: F
authors: Paris
authors: François M
authors: FM
authors: Vallette
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000528:radiation effects; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D005260:Female; D005720:Gamma Rays; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism* / Q000528:radiation effects; D008875:Middle Aged