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

Authors

Xiaojing Cui, University of KentuckyFollow
Cuiping Zhang, University of KentuckyFollow
Fang Wang, University of Kentucky
Xinghui Zhao, University of Kentucky
Shuxia Wang, University of KentuckyFollow
Jinpeng Liu, University of KentuckyFollow
Daheng He, University of KentuckyFollow
Chi Wang, University of KentuckyFollow
Feng-Chun Yang, University of Texas Health Science Center at San Antonio
Sheng Tong, University of KentuckyFollow
Ying Liang, University of KentuckyFollow

Abstract

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 micro- RNA 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

Document Type

Article

Publication Date

3-2023

Notes/Citation Information

© 2023 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Digital Object Identifier (DOI)

https://doi.org/10.1016/j.celrep.2023.112274

Funding Information

The authors are supported by the National Institutes of Health under awards R01HL124015 (Y.L.) and R21HL140213 (Y.L.) and the Markey Cancer Center’s Flow Cytometry and Immune Monitoring Core and Biostatistics and Bioinformatics Shared Resource Facilities (P30CA177558). We thank the Markey Cancer Center’s Research Communications Office for editing and graphics support.

Repository Citation

Cui, Xiaojing; Zhang, Cuiping; Wang, Fang; Zhao, Xinghui; Wang, Shuxia; Liu, Jinpeng; He, Daheng; Wang, Chi; Yang, Feng-Chun; Tong, Sheng; and Liang, Ying, "Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1" (2023). Markey Cancer Center Faculty Publications. 356.
https://uknowledge.uky.edu/markey_facpub/356