Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1
Summary: 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...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2023-03-01
|
| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124723002851 |
| _version_ | 1797867669541617664 |
|---|---|
| author | Xiaojing Cui Cuiping Zhang Fang Wang Xinghui Zhao Shuxia Wang Jinpeng Liu Daheng He Chi Wang Feng-Chun Yang Sheng Tong Ying Liang |
| author_facet | Xiaojing Cui Cuiping Zhang Fang Wang Xinghui Zhao Shuxia Wang Jinpeng Liu Daheng He Chi Wang Feng-Chun Yang Sheng Tong Ying Liang |
| author_sort | Xiaojing Cui |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-09T23:43:50Z |
| format | Article |
| id | doaj.art-7de43e04dde14bda914cd6152aa78600 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-09T23:43:50Z |
| publishDate | 2023-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7de43e04dde14bda914cd6152aa786002023-03-18T04:40:55ZengElsevierCell Reports2211-12472023-03-01423112274Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1Xiaojing Cui0Cuiping Zhang1Fang Wang2Xinghui Zhao3Shuxia Wang4Jinpeng Liu5Daheng He6Chi Wang7Feng-Chun Yang8Sheng Tong9Ying Liang10Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536 USADepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536 USADepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536 USADepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536 USADepartment of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536 USADivision of Cancer Biostatistics, Department of Internal Medicine, University of Kentucky, Lexington, KY 40536 USADivision of Cancer Biostatistics, Department of Internal Medicine, University of Kentucky, Lexington, KY 40536 USADivision of Cancer Biostatistics, Department of Internal Medicine, University of Kentucky, Lexington, KY 40536 USADepartment of Cell Systems & Anatomy, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA; Mays Cancer Center, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USADepartment of Bioengineering, University of Kentucky, Lexington, KY 40536, USADepartment of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536 USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124723002851CP: Developmental biology |
| spellingShingle | Xiaojing Cui Cuiping Zhang Fang Wang Xinghui Zhao Shuxia Wang Jinpeng Liu Daheng He Chi Wang Feng-Chun Yang Sheng Tong Ying Liang Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1 Cell Reports CP: Developmental biology |
| title | Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1 |
| title_full | Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1 |
| title_fullStr | Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1 |
| title_full_unstemmed | Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1 |
| title_short | Latexin regulates sex dimorphism in hematopoiesis via gender-specific differential expression of microRNA 98-3p and thrombospondin 1 |
| title_sort | latexin regulates sex dimorphism in hematopoiesis via gender specific differential expression of microrna 98 3p and thrombospondin 1 |
| topic | CP: Developmental biology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124723002851 |
| work_keys_str_mv | AT xiaojingcui latexinregulatessexdimorphisminhematopoiesisviagenderspecificdifferentialexpressionofmicrorna983pandthrombospondin1 AT cuipingzhang latexinregulatessexdimorphisminhematopoiesisviagenderspecificdifferentialexpressionofmicrorna983pandthrombospondin1 AT fangwang latexinregulatessexdimorphisminhematopoiesisviagenderspecificdifferentialexpressionofmicrorna983pandthrombospondin1 AT xinghuizhao latexinregulatessexdimorphisminhematopoiesisviagenderspecificdifferentialexpressionofmicrorna983pandthrombospondin1 AT shuxiawang latexinregulatessexdimorphisminhematopoiesisviagenderspecificdifferentialexpressionofmicrorna983pandthrombospondin1 AT jinpengliu latexinregulatessexdimorphisminhematopoiesisviagenderspecificdifferentialexpressionofmicrorna983pandthrombospondin1 AT dahenghe latexinregulatessexdimorphisminhematopoiesisviagenderspecificdifferentialexpressionofmicrorna983pandthrombospondin1 AT chiwang latexinregulatessexdimorphisminhematopoiesisviagenderspecificdifferentialexpressionofmicrorna983pandthrombospondin1 AT fengchunyang latexinregulatessexdimorphisminhematopoiesisviagenderspecificdifferentialexpressionofmicrorna983pandthrombospondin1 AT shengtong latexinregulatessexdimorphisminhematopoiesisviagenderspecificdifferentialexpressionofmicrorna983pandthrombospondin1 AT yingliang latexinregulatessexdimorphisminhematopoiesisviagenderspecificdifferentialexpressionofmicrorna983pandthrombospondin1 |