Fine-Tuning of Cholesterol Homeostasis Controls Erythroid Differentiation.

ABSTRACT: Lipid metabolism is essential for stemness maintenance, self-renewal, and differentiation of stem cells, however, the regulatory function of cholesterol metabolism in erythroid differentiation is poorly studied. In the present study, a critical role for cholesterol homeostasis in terminal erythropoiesis is uncovered. The master transcriptional factor GATA1 binds to Sterol-regulatory element binding protein 2 (SREBP2) to downregulate cholesterol biosynthesis, leading to a gradual reduction in intracellular cholesterol levels. It is further shown that reduced cholesterol functions to block erythroid proliferation via the cholesterol/mTORC1/ribosome biogenesis axis, which coordinates cell cycle exit in the late stages of erythroid differentiation. The interaction of GATA1 and SREBP2 also prov

SUBMITTER: Lu Z 

PROVIDER: S-EPMC8805577 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature