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Direct Reprogramming of Mouse Fibroblasts toward Leydig-like Cells by Defined Factors

Leydig cells (LCs) play crucial roles in producing testosterone, and their dysfunction leads to male hypogonadism. LC transplantation is a promising alternative therapy for male hypogonadism. However, the source of LCs limits this strategy for clinical applications. Here, we report our success in re...

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Autores principales: Yang, Yan, Li, Ziyi, Wu, Xupeng, Chen, Haolin, Xu, Wenting, Xiang, Qi, Zhang, Qihao, Chen, Jie, Ge, Ren-Shan, Su, Zhijian, Huang, Yadong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233410/
https://www.ncbi.nlm.nih.gov/pubmed/28017657
http://dx.doi.org/10.1016/j.stemcr.2016.11.010
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author Yang, Yan
Li, Ziyi
Wu, Xupeng
Chen, Haolin
Xu, Wenting
Xiang, Qi
Zhang, Qihao
Chen, Jie
Ge, Ren-Shan
Su, Zhijian
Huang, Yadong
author_facet Yang, Yan
Li, Ziyi
Wu, Xupeng
Chen, Haolin
Xu, Wenting
Xiang, Qi
Zhang, Qihao
Chen, Jie
Ge, Ren-Shan
Su, Zhijian
Huang, Yadong
author_sort Yang, Yan
collection PubMed
description Leydig cells (LCs) play crucial roles in producing testosterone, and their dysfunction leads to male hypogonadism. LC transplantation is a promising alternative therapy for male hypogonadism. However, the source of LCs limits this strategy for clinical applications. Here, we report our success in reprogramming mice fibroblasts into LCs by expressing three transcriptional factors, Dmrt1, Gata4, and Nr5a1. The induced Leydig-like cells (iLCs) expressed steroidogenic genes, had a global gene expression profile similar to that of adult LCs, and acquired androgen synthesis capabilities. When iLCs were transplanted into rats or mice testes that were selectively depleted of endogenous LCs, the transplanted cells could survive and function in the interstitium of testis, resulting in the restoration of normal levels of serum testosterone. These findings demonstrate that the fibroblasts were able to be directly converted into iLCs by few defined factors, which may facilitate future applications in regenerative medicine.
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spelling pubmed-52334102017-01-23 Direct Reprogramming of Mouse Fibroblasts toward Leydig-like Cells by Defined Factors Yang, Yan Li, Ziyi Wu, Xupeng Chen, Haolin Xu, Wenting Xiang, Qi Zhang, Qihao Chen, Jie Ge, Ren-Shan Su, Zhijian Huang, Yadong Stem Cell Reports Article Leydig cells (LCs) play crucial roles in producing testosterone, and their dysfunction leads to male hypogonadism. LC transplantation is a promising alternative therapy for male hypogonadism. However, the source of LCs limits this strategy for clinical applications. Here, we report our success in reprogramming mice fibroblasts into LCs by expressing three transcriptional factors, Dmrt1, Gata4, and Nr5a1. The induced Leydig-like cells (iLCs) expressed steroidogenic genes, had a global gene expression profile similar to that of adult LCs, and acquired androgen synthesis capabilities. When iLCs were transplanted into rats or mice testes that were selectively depleted of endogenous LCs, the transplanted cells could survive and function in the interstitium of testis, resulting in the restoration of normal levels of serum testosterone. These findings demonstrate that the fibroblasts were able to be directly converted into iLCs by few defined factors, which may facilitate future applications in regenerative medicine. Elsevier 2016-12-22 /pmc/articles/PMC5233410/ /pubmed/28017657 http://dx.doi.org/10.1016/j.stemcr.2016.11.010 Text en © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Yang, Yan
Li, Ziyi
Wu, Xupeng
Chen, Haolin
Xu, Wenting
Xiang, Qi
Zhang, Qihao
Chen, Jie
Ge, Ren-Shan
Su, Zhijian
Huang, Yadong
Direct Reprogramming of Mouse Fibroblasts toward Leydig-like Cells by Defined Factors
title Direct Reprogramming of Mouse Fibroblasts toward Leydig-like Cells by Defined Factors
title_full Direct Reprogramming of Mouse Fibroblasts toward Leydig-like Cells by Defined Factors
title_fullStr Direct Reprogramming of Mouse Fibroblasts toward Leydig-like Cells by Defined Factors
title_full_unstemmed Direct Reprogramming of Mouse Fibroblasts toward Leydig-like Cells by Defined Factors
title_short Direct Reprogramming of Mouse Fibroblasts toward Leydig-like Cells by Defined Factors
title_sort direct reprogramming of mouse fibroblasts toward leydig-like cells by defined factors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5233410/
https://www.ncbi.nlm.nih.gov/pubmed/28017657
http://dx.doi.org/10.1016/j.stemcr.2016.11.010
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