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.

造血干细胞 (HSC) 具有自我更新和分化为所有血细胞类型的能力。HSC 及其分化后代表现出性别差异。基本机制在很大程度上仍未被探索。我们之前报道过，乳胶蛋白 ( Lxn ) 缺失可增加雌性小鼠 HSC 的存活率和增殖能力。在这里，我们发现Lxn敲除 ( Lxn ^−/− ) 雄性小鼠在生理和骨髓抑制条件下的 HSC 功能和造血功能没有差异。我们进一步发现，女性 HSC 中 Lxn 的下游靶基因Thbs1在男性 HSC 中受到抑制。男性特异性的 microRNA 98-3p (miR98-3p) 高表达有助于抑制雄性 HSC 中的Thbs1 ，从而消除Lxn在雄性 HSC 和造血中的功能作用。这些发现揭示了涉及性染色体相关 microRNA 的调节机制及其对造血中Lxn-Thbs1信号传导的差异控制，并揭示了正常和恶性造血中性别二态性的潜在过程。