Direct reprogramming of fibroblasts into embryonic sertoli-like cells by defined factors

Yosef Buganim*, Elena Itskovich, Yueh Chiang Hu, Albert W. Cheng, Kibibi Ganz, Sovan Sarkar, Dongdong Fu, G. Grant Welstead, David C. Page, Rudolf Jaenisch

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

136 Scopus citations


Sertoli cells are considered the "supporting cells" of the testis that play an essential role in sex determination during embryogenesis and in spermatogenesis during adulthood. Their essential roles in male fertility along with their immunosuppressive and neurotrophic properties make them an attractive cell type for therapeutic applications. Here we demonstrate the generation of induced embryonic Sertoli-like cells (ieSCs) by ectopic expression of five transcription factors. We characterize the role of specific transcription factor combinations in the transition from fibroblasts to ieSCs and identify key steps in the process. Initially, transduced fibroblasts underwent a mesenchymal to epithelial transition and then acquired the ability to aggregate, formed tubular-like structures, and expressed embryonic Sertoli-specific markers. These Sertoli-like cells facilitated neuronal differentiation and self-renewal of neural progenitor cells (NPCs), supported the survival of germ cells in culture, and cooperated with endogenous embryonic Sertoli and primordial germ cells in the generation of testicular cords in the fetal gonad.

Original languageAmerican English
Pages (from-to)373-386
Number of pages14
JournalCell Stem Cell
Issue number3
StatePublished - 7 Sep 2012
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health Grants R37-CA084198 and RO1-HD045022 (R.J.) and the Howard Hughes Medical Institute (D.C.P. and Y.-C.H). We thank Y. Katz for technical assistance and for commenting on the manuscript. We also thank W.C. Salmon for microscopy assistance.


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