Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4
Sertoli cells are essential nurse cells in the testis that regulate the process of spermatogenesis and establish the immune-privileged environment of the blood-testis-barrier (BTB). Here, we report the in vitro reprogramming of fibroblasts to human induced Sertoli-like cells (hiSCs). Initially, five...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2019-11-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/48767 |
| _version_ | 1811199761736269824 |
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| author | Jianlin Liang Nan Wang Jing He Jian Du Yahui Guo Lin Li Wenbo Wu Chencheng Yao Zheng Li Kehkooi Kee |
| author_facet | Jianlin Liang Nan Wang Jing He Jian Du Yahui Guo Lin Li Wenbo Wu Chencheng Yao Zheng Li Kehkooi Kee |
| author_sort | Jianlin Liang |
| collection | DOAJ |
| description | Sertoli cells are essential nurse cells in the testis that regulate the process of spermatogenesis and establish the immune-privileged environment of the blood-testis-barrier (BTB). Here, we report the in vitro reprogramming of fibroblasts to human induced Sertoli-like cells (hiSCs). Initially, five transcriptional factors and a gene reporter carrying the AMH promoter were utilized to obtain the hiSCs. We further reduce the number of reprogramming factors to two, NR5A1 and GATA4, and show that these hiSCs have transcriptome profiles and cellular properties that are similar to those of primary human Sertoli cells. Moreover, hiSCs can sustain the viability of spermatogonia cells harvested from mouse seminiferous tubules. hiSCs suppress the proliferation of human T lymphocytes and protect xenotransplanted human cells in mice with normal immune systems. hiSCs also allow us to determine a gene associated with Sertoli cell only syndrome (SCO), CX43, is indeed important in regulating the maturation of Sertoli cells. |
| first_indexed | 2024-04-12T01:52:45Z |
| format | Article |
| id | doaj.art-7e219e7093304fa689822a7e2fee9550 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T01:52:45Z |
| publishDate | 2019-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7e219e7093304fa689822a7e2fee95502022-12-22T03:52:53ZengeLife Sciences Publications LtdeLife2050-084X2019-11-01810.7554/eLife.48767Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4Jianlin Liang0https://orcid.org/0000-0003-3027-2421Nan Wang1Jing He2Jian Du3Yahui Guo4Lin Li5Wenbo Wu6Chencheng Yao7Zheng Li8Kehkooi Kee9https://orcid.org/0000-0001-6926-7203Center for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China; Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, ChinaCenter for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, ChinaCenter for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, ChinaCenter for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, ChinaCenter for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, ChinaCenter for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, ChinaNational Institute of Biological Sciences, Beijing, ChinaDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai General Hospital, Shanghai, ChinaDepartment of Andrology, the Center for Men's Health, Urologic Medical Center, Shanghai Key Laboratory of Reproductive Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai General Hospital, Shanghai, ChinaCenter for Stem Cell Biology and Regenerative Medicine, Department of Basic Medical Sciences, School of Medicine, Tsinghua University, Beijing, China; Tsinghua-Peking Center for Life Sciences, School of Life Sciences, Tsinghua University, Beijing, China; Beijing Advanced Innovation Center for Structural Biology, School of Life Sciences, Tsinghua University, Beijing, ChinaSertoli cells are essential nurse cells in the testis that regulate the process of spermatogenesis and establish the immune-privileged environment of the blood-testis-barrier (BTB). Here, we report the in vitro reprogramming of fibroblasts to human induced Sertoli-like cells (hiSCs). Initially, five transcriptional factors and a gene reporter carrying the AMH promoter were utilized to obtain the hiSCs. We further reduce the number of reprogramming factors to two, NR5A1 and GATA4, and show that these hiSCs have transcriptome profiles and cellular properties that are similar to those of primary human Sertoli cells. Moreover, hiSCs can sustain the viability of spermatogonia cells harvested from mouse seminiferous tubules. hiSCs suppress the proliferation of human T lymphocytes and protect xenotransplanted human cells in mice with normal immune systems. hiSCs also allow us to determine a gene associated with Sertoli cell only syndrome (SCO), CX43, is indeed important in regulating the maturation of Sertoli cells.https://elifesciences.org/articles/48767human cell linesSertoli cellsmouse |
| spellingShingle | Jianlin Liang Nan Wang Jing He Jian Du Yahui Guo Lin Li Wenbo Wu Chencheng Yao Zheng Li Kehkooi Kee Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4 eLife human cell lines Sertoli cells mouse |
| title | Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4 |
| title_full | Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4 |
| title_fullStr | Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4 |
| title_full_unstemmed | Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4 |
| title_short | Induction of Sertoli-like cells from human fibroblasts by NR5A1 and GATA4 |
| title_sort | induction of sertoli like cells from human fibroblasts by nr5a1 and gata4 |
| topic | human cell lines Sertoli cells mouse |
| url | https://elifesciences.org/articles/48767 |
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