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Bcl2 overexpression rescues the hematopoietic stem cell defects in Ku70-deficient mice by restoration of quiescence.

ABSTRACT: DNA repair is essential for hematopoietic stem cell (HSC) maintenance. Ku70 is a key component of the nonhomologous end-joining pathway, which is the major pathway for DNA double-strand break repair. We find that HSCs from Ku70-deficient mice are severely defective in self-renewal, competitive repopulation, and bone marrow (BM) hematopoietic niche occupancy and that loss of quiescence results in a dramatic defect in the maintenance of Ku70-deficient HSCs. Interestingly, although overexpression of Bcl2 does not rescue the severe combined immunodeficiency phenotype in Ku70-deficient mice, overexpression of Bcl2 in Ku70-deficient HSCs almost completely rescued the impaired HSC quiescence, repopulation, and BM hematopoietic niche occupancy capacities. Together, our data indicate that the HSC maintenance defect of Ku70-deficient mice is due to the loss of HSC quiescent populations, whereas overexpression of Bcl2 rescues the HSC defect in Ku70-deficient mice by restoration of quiescence. Our study uncovers a novel role of Bcl2 in HSC quiescence regulation.

SUBMITTER: Qing Y

PROVIDER: S-EPMC3924923 | biostudies-literature |

REPOSITORIES: biostudies-literature

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