Sexual dimorphism in the mouse bone marrow niche regulates hematopoietic engraftment via sex-specific Kdm5c/Cxcl12 signaling.

ABSTRACT: The bone marrow (BM) niche is critical in regulating hematopoiesis, and sexual dimorphism and its underlying mechanism in the BM niche and its impact on hematopoiesis are not well understood. We show that male mice exhibited a higher abundance of leptin-receptor-expressing mesenchymal stromal cells (LepR-MSCs) compared with female mice. Sex-mismatched coculture and BM transplantation showed that the male BM niche provided superior support for in vitro colony formation and in vivo hematopoietic engraftment. The cotransplantation of male stromal cells significantly enhanced engraftment in female recipients. Single-cell RNA-seq revealed that the lower expression of the X-linked lysine H3K4 demethylase, Kdm5c, in male MSCs led to the increased expression of Cxcl12. In MSC-specific Kdm5c-KO mou

SUBMITTER: Cui X 

PROVIDER: S-EPMC11870739 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature