PLAG1 dampens protein synthesis to promote human hematopoietic stem cell self-renewal.

ABSTRACT: Hematopoietic stem cell (HSC) dormancy is understood as supportive of HSC function and its long-term integrity. Although regulation of stress responses incurred as a result of HSC activation is recognized as important in maintaining stem cell function, little is understood of the preventive machinery present in human HSCs that may serve to resist their activation and promote HSC self-renewal. We demonstrate that the transcription factor PLAG1 is essential for long-term HSC function and, when overexpressed, endows a 15.6-fold enhancement in the frequency of functional HSCs in stimulatory conditions. Genome-wide measures of chromatin occupancy and PLAG1-directed gene expression changes combined with functional measures reveal that PLAG1 dampens protein synthesis, restrains cell growth and di

SUBMITTER: Keyvani Chahi A 

PROVIDER: S-EPMC9437713 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature