造血干细胞 (HSCs) 具有自我更新和分化成所有血细胞类型的能力。HSCs 及其分化后代显示性别/性别差异。根本机制仍然大多未被探索。我们之前报告称，橡胶素酰胺酶 (Lxn) 缺失增加了雌性小鼠中 HSC 存活和再生能力。在此，我们发现在生理和造血抑制条件下，Lxn 缺失 (Lxn-/-) 雄性小鼠的 HSC 功能和造血过程没有差异。我们进一步发现，Thbs1，Lxn 的下游靶基因在雄性 HSC 中受到抑制。雄性特异性高表达的微RNA 98-3p (miR98-3p) 有助于 Thbs1 在雄性 HSC 中的抑制，从而消除了 Lxn 在雄性 HSC 和造血过程中的功能影响。这些发现揭示了一个涉及性染色体相关微RNA及其在造血过程中对 Lxn-Thbs1 信号的差异性调控的调节机制，为正常和恶性造血过程中的性异形成过程提供了启示。版权所有©2023 Elsevier Inc.。保留所有权利。

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.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.