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

Xiaojing Cui; Cuiping Zhang; Fang Wang; Xinghui Zhao; Shuxia Wang; Jinpeng Liu; Daheng He; Chi Wang; Feng Chun Yang; Sheng Tong; Ying Liang

doi:10.1016/j.celrep.2023.112274

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

Xiaojing Cui, Cuiping Zhang, Fang Wang, Xinghui Zhao, Shuxia Wang, Jinpeng Liu, Daheng He, Chi Wang, Feng Chun Yang, Sheng Tong, Ying Liang

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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 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.

Original language	English
Article number	112274
Journal	Cell Reports
Volume	42
Issue number	3
DOIs	https://doi.org/10.1016/j.celrep.2023.112274
State	Published - Mar 28 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Funding

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.

Funders	Funder number
National Institutes of Health (NIH)	R01HL124015, R21HL140213
National Institutes of Health (NIH)
University of Kentucky Markey Cancer Center	P30CA177558
University of Kentucky Markey Cancer Center

Keywords

CP: Developmental biology
Thbs1
gender difference
hematopoiesis
hematopoietic stem cell
latexin
microRNA98-3p
sex dimorphism

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.celrep.2023.112274

Cite this

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

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 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.",

keywords = "CP: Developmental biology, Thbs1, gender difference, hematopoiesis, hematopoietic stem cell, latexin, microRNA98-3p, sex dimorphism",

author = "Xiaojing Cui and Cuiping Zhang and Fang Wang and Xinghui Zhao and Shuxia Wang and Jinpeng Liu and Daheng He and Chi Wang and Yang, {Feng Chun} and Sheng Tong and Ying Liang",

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AU - Cui, Xiaojing

AU - Zhang, Cuiping

AU - Wang, Fang

AU - Zhao, Xinghui

AU - Wang, Shuxia

AU - Liu, Jinpeng

AU - He, Daheng

AU - Wang, Chi

AU - Yang, Feng Chun

AU - Tong, Sheng

AU - Liang, Ying

PY - 2023/3/28

Y1 - 2023/3/28

N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

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