Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development
Abstract Testis-specific transcript 10 (Tex10) is highly expressed in the testis, embryonic stem cells (ESCs), and primordial germ cells (PGCs). We previously generated a Tex10 knockout mouse model demonstrating its critical roles in ESC pluripotency and preimplantation development. Here, using cond...
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Nature Portfolio
2025-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-57165-2 |
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| author | Feifei Yuan Jihong Yang Fanglin Ma Zhe Hu Vikas Malik Ruge Zang Dan Li Xianle Shi Xin Huang Hongwei Zhou Jianlong Wang |
| author_facet | Feifei Yuan Jihong Yang Fanglin Ma Zhe Hu Vikas Malik Ruge Zang Dan Li Xianle Shi Xin Huang Hongwei Zhou Jianlong Wang |
| author_sort | Feifei Yuan |
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| description | Abstract Testis-specific transcript 10 (Tex10) is highly expressed in the testis, embryonic stem cells (ESCs), and primordial germ cells (PGCs). We previously generated a Tex10 knockout mouse model demonstrating its critical roles in ESC pluripotency and preimplantation development. Here, using conditional knockout mice and dTAG-degron ESCs, we show Tex10 is required for spermatogenesis and ESC-to-PGCLC differentiation. Specifically, Tex10-null spermatocytes arrest at metaphase I, compromising round spermatid formation. Tex10 depletion and overexpression compromise and enhance ESC-to-PGCLC differentiation, respectively. Mechanistically, bulk and single-cell RNA sequencing reveals that Tex10 depletion downregulates genes involved in pluripotency, PGC development, and spermatogenesis while upregulating genes promoting somatic programs. Chromatin occupancy study reveals that Tex10 binds to H3K4me3-marked promoters of Psmd3 and Psmd7, negative regulators of Wnt signaling, and activates their expression, thereby restraining Wnt signaling. Our study identifies Tex10 as a previously unappreciated factor in spermatogenesis and PGC development, offering potential therapeutic insights for treating male infertility. |
| format | Article |
| id | doaj-art-777f7766975a41b2bfe8f55c2757a5ca |
| institution | OA Journals |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
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| series | Nature Communications |
| spelling | doaj-art-777f7766975a41b2bfe8f55c2757a5ca2025-08-20T02:01:38ZengNature PortfolioNature Communications2041-17232025-02-0116112210.1038/s41467-025-57165-2Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell developmentFeifei Yuan0Jihong Yang1Fanglin Ma2Zhe Hu3Vikas Malik4Ruge Zang5Dan Li6Xianle Shi7Xin Huang8Hongwei Zhou9Jianlong Wang10Department of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterDepartment of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterDepartment of Cell, Developmental and Regenerative Biology; The Black Family Stem Cell Institute, Icahn School of Medicine at Mount SinaiDepartment of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterDepartment of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterDepartment of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterDepartment of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterDepartment of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterDepartment of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterDepartment of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterDepartment of Medicine, Columbia Center for Human Development and Stem Cell Therapies, Columbia Stem Cell Initiative, Herbert Irving Comprehensive Cancer Center, Columbia University Irving Medical CenterAbstract Testis-specific transcript 10 (Tex10) is highly expressed in the testis, embryonic stem cells (ESCs), and primordial germ cells (PGCs). We previously generated a Tex10 knockout mouse model demonstrating its critical roles in ESC pluripotency and preimplantation development. Here, using conditional knockout mice and dTAG-degron ESCs, we show Tex10 is required for spermatogenesis and ESC-to-PGCLC differentiation. Specifically, Tex10-null spermatocytes arrest at metaphase I, compromising round spermatid formation. Tex10 depletion and overexpression compromise and enhance ESC-to-PGCLC differentiation, respectively. Mechanistically, bulk and single-cell RNA sequencing reveals that Tex10 depletion downregulates genes involved in pluripotency, PGC development, and spermatogenesis while upregulating genes promoting somatic programs. Chromatin occupancy study reveals that Tex10 binds to H3K4me3-marked promoters of Psmd3 and Psmd7, negative regulators of Wnt signaling, and activates their expression, thereby restraining Wnt signaling. Our study identifies Tex10 as a previously unappreciated factor in spermatogenesis and PGC development, offering potential therapeutic insights for treating male infertility.https://doi.org/10.1038/s41467-025-57165-2 |
| spellingShingle | Feifei Yuan Jihong Yang Fanglin Ma Zhe Hu Vikas Malik Ruge Zang Dan Li Xianle Shi Xin Huang Hongwei Zhou Jianlong Wang Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development Nature Communications |
| title | Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development |
| title_full | Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development |
| title_fullStr | Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development |
| title_full_unstemmed | Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development |
| title_short | Pluripotency factor Tex10 finetunes Wnt signaling for spermatogenesis and primordial germ cell development |
| title_sort | pluripotency factor tex10 finetunes wnt signaling for spermatogenesis and primordial germ cell development |
| url | https://doi.org/10.1038/s41467-025-57165-2 |
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