Bifurcate Regulation of Hematopoietic Homeostasis and Bone Osteogenesis by VHL-HIF2α-Controlled Adipocyte Function.

ABSTRACT: Adipocytes play a pivotal role in maintaining metabolic and immunological homeostasis. Here, this work shows that VHL-HIF2α (VHL is Von Hippel-Lindau) axis in mature adipocytes regulates hematopoiesis and osteogenesis. Genetic ablation of VHL in adipocytes triggers profound systemic autoinflammation and abnormal hematopoiesis, concomitant with fat mass decrease and pathological elevation of bone mass. On one hand, VHL deficiency results in aberrantly high stem cell factor (SCF) expression in adipocytes, which exerts a negative role for hematopoietic homeostasis through disrupting hematopoietic stem cell (HSC) quiescence. In vivo anti-CD117 monoclonal antibody treatment ameliorates the hematopoietic defects in VHL-deficient mice. On the other hand, direct HIF2α binding to hypoxia-response e

SUBMITTER: Li Q 

PROVIDER: S-EPMC12850111 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature