Role of c-Myc haploinsufficiency in the maintenance of HSCs in mice.

ABSTRACT: This study was conducted to determine the dosage effect of c-Myc on hematopoiesis and its distinct role in mediating the Wnt/β-catenin pathway in hematopoietic stem cell (HSC) and bone marrow niche cells. c-Myc haploinsufficiency led to ineffective hematopoiesis by inhibiting HSC self-renewal and quiescence and by promoting apoptosis. We have identified Nr4a1, Nr4a2, and Jmjd3, which are critical for the maintenance of HSC functions, as previously unrecognized downstream targets of c-Myc in HSCs. c-Myc directly binds to the promoter regions of Nr4a1, Nr4a2, and Jmjd3 and regulates their expression. Our results revealed that Nr4a1 and Nr4a2 mediates the function of c-Myc in regulating HSC quiescence, whereas all 3 genes contribute to the function of c-Myc in the maintenance of HSC survival.

SUBMITTER: Sheng Y 

PROVIDER: S-EPMC8215193 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature