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

Yan Yang, Ziyi Li, Xupeng Wu, Haolin Chen, Wenting Xu, Qi Xiang, Qihao Zhang, Jie Chen, Ren Shan Ge, Zhijian Su, Yadong Huang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)39-53
Number of pages15
JournalStem Cell Reports
Volume8
Issue number1
DOIs
StatePublished - Jan 10 2017

Keywords

  • Leydig cell
  • cell fate conversion
  • fibroblast
  • transcription factors

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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