Sustained PU.1 levels balance cell-cycle regulators to prevent exhaustion of adult hematopoietic stem cells.

ABSTRACT: To provide a lifelong supply of blood cells, hematopoietic stem cells (HSCs) need to carefully balance both self-renewing cell divisions and quiescence. Although several regulators that control this mechanism have been identified, we demonstrate that the transcription factor PU.1 acts upstream of these regulators. So far, attempts to uncover PU.1's role in HSC biology have failed because of the technical limitations of complete loss-of-function models. With the use of hypomorphic mice with decreased PU.1 levels specifically in phenotypic HSCs, we found reduced HSC long-term repopulation potential that could be rescued completely by restoring PU.1 levels. PU.1 prevented excessive HSC division and exhaustion by controlling the transcription of multiple cell-cycle regulators. Levels of PU.1 w

SUBMITTER: Staber PB 

PROVIDER: S-EPMC3644723 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature