title: Direct reprogramming of fibroblasts into embryonic Sertoli-like cells by defined factors.
abstract: 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.
authors.affiliation: Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, MA 02142, USA. yossib@wi.mit.edu
authors.forename: Yosef
authors.initials: Y
authors.lastname: Buganim
authors.forename: Elena
authors.initials: E
authors.lastname: Itskovich
authors.forename: Yueh-Chiang
authors.initials: YC
authors.lastname: Hu
authors.forename: Albert W
authors.initials: AW
authors.lastname: Cheng
authors.forename: Kibibi
authors.initials: K
authors.lastname: Ganz
authors.forename: Sovan
authors.initials: S
authors.lastname: Sarkar
authors.forename: Dongdong
authors.initials: D
authors.lastname: Fu
authors.forename: G Grant
authors.initials: GG
authors.lastname: Welstead
authors.forename: David C
authors.initials: DC
authors.lastname: Page
authors.forename: Rudolf
authors.initials: R
authors.lastname: Jaenisch
mesh_terms: D000818:Animals; D002449:Cell Aggregation / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D065150:Cellular Reprogramming / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D050991:GATA4 Transcription Factor / Q000378:metabolism; D020869:Gene Expression Profiling; D007621:Karyotyping; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000378:metabolism; D012708:Sertoli Cells / Q000166:cytology* / Q000378:metabolism; D054339:Steroidogenic Factor 1 / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000196:embryology; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C110547:DMRT1 protein; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D055758:SOX9 Transcription Factor; C527933:Sox9 protein, mouse; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse; D019859:Proto-Oncogene Proteins c-met