Open AccessDifferentiation‐Related Response to DNA Breaks in Human Mesenchymal Stem Cells
Author(s) -
Oliver Lisa,
Hue Erika,
Séry Quentin,
Lafargue Audrey,
Pecqueur Claire,
Paris François,
Vallette François M.
Publication year - 2013
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1336
Subject(s) - ku70 , mesenchymal stem cell , biology , dna damage , microbiology and biotechnology , apoptosis , dna repair , stem cell , cellular differentiation , dna , cancer research , genetics , gene
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. S TEM C ELLS 2013;31:800–807