Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1.

Hematopoietic stem cells (HSCs) have the ability to self-renew and differentiate to all blood cell types. HSCs and their differentiated progeny show sex/gender differences. The fundamental mechanisms remain largely unexplored. We previously reported that latexin (Lxn) deletion increased HSC survival and repopulation capacity in female mice. Here, we find no differences in HSC function and hematopoiesis in Lxn knockout (Lxn ^−/−) male mice under physiologic and myelosuppressive conditions. We further find that Thbs1 , a downstream target gene of Lxn in female HSCs, is repressed in male HSCs. Male-specific high expression of microRNA 98-3p (miR98-3p) contributes to Thbs1 suppression in male HSCs, thus abrogating the functional effect of Lxn in male HSCs and hematopoiesis. These findings uncover a regulatory mechanism involving a sex-chromosome-related microRNA and its differential control of Lxn-Thbs1 signaling in hematopoiesis and shed light on the process underlying sex dimorphism in both normal and malignant hematopoiesis. [Display omitted] • Latexin deletion does not have functional effects on HSCs and hematopoiesis in male mice • Male-specific suppression of Thbs1 underlies latexin-mediated hematopoiesis sex dimorphism • Male-specific high expression of microRNA98-3p leads to Thbs1 downregulation in male HSCs • Thbs1 reduction eliminates latexin's functional action on male HSCs and hematopoiesis In both normal and pathological conditions, blood-forming stem cell activity and the blood system exhibit gender differences. Cui et al. discover that the latexin/microRNA-Thbs1 signaling pathway contributes to such differences between males and females and is responsible for hematopoiesis sex dimorphism. [ABSTRACT FROM AUTHOR]