Cholesterol confers ferroptosis resistance onto myeloid-biased hematopoietic stem cells and prevents irradiation-induced myelosuppression.

ABSTRACT: There is growing appreciation that hematopoietic alterations underpin the ubiquitous detrimental effects of metabolic disorders. The susceptibility of bone marrow (BM) hematopoiesis to perturbations of cholesterol metabolism is well documented, while the underlying cellular and molecular mechanisms remain poorly understood. Here we reveal a distinct and heterogeneous cholesterol metabolic signature within BM hematopoietic stem cells (HSCs). We further show that cholesterol directly regulates maintenance and lineage differentiation of long-term HSCs (LT-HSCs), with high levels of intracellular cholesterol favoring maintenance and myeloid bias of LT-HSCs. During irradiation-induced myelosuppression, cholesterol also safeguards LT-HSC maintenance and myeloid regeneration. Mechanistically, we

SUBMITTER: Liu C 

PROVIDER: S-EPMC10025135 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature