title: Direct Reprogramming of Mouse Fibroblasts toward Leydig-like Cells by Defined Factors.
abstract: 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.
authors.affiliation: Department of Cell Biology, Jinan University, Guangzhou 510632, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Cell Biology, Jinan University, Guangzhou 510632, China.
authors.forename: Ziyi
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Cell Biology, Jinan University, Guangzhou 510632, China.
authors.forename: Xupeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MA 21205, USA; Center of Scientific Research, the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Haolin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Pharmacology, Jinan University, Guangzhou 510632, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Cell Biology, Jinan University, Guangzhou 510632, China; Department of Pharmacology, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiang
authors.affiliation: Department of Cell Biology, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China.
authors.forename: Qihao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Urinary Surgery, First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Center of Scientific Research, the Second Affiliated Hospital & Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, China.
authors.forename: Ren-Shan
authors.initials: RS
authors.lastname: Ge
authors.affiliation: Department of Cell Biology, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China. Electronic address: tjnuszj@jnu.edu.cn.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Cell Biology, Jinan University, Guangzhou 510632, China; Department of Pharmacology, Jinan University, Guangzhou 510632, China; Guangdong Province Key Laboratory of Bioengineering Medicine, Guangzhou 510632, China. Electronic address: tydhuang@jnu.edu.cn.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics; D002460:Cell Line; D054338:Cell Transdifferentiation / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics; D016000:Cluster Analysis; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism* / Q000637:transplantation; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D007985:Leydig Cells / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic; D051381:Rats; D013739:Testosterone / Q000097:blood; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome
chemical_list: C110547:DMRT1 protein; D014157:Transcription Factors; D013739:Testosterone
keywords: Leydig cell; cell fate conversion; fibroblast; transcription factors