Direct Reprogramming of Fibroblasts into Embryonic Sertoli-like Cells by Defined Factors

被引：153

作者：

Buganim, Yosef ^{[1
]}

Itskovich, Elena ^{[1
]}

Hu, Yueh-Chiang ^{[1
,3
]}

Cheng, Albert W. ^{[1
,2
]}

Ganz, Kibibi ^{[1
]}

Sarkar, Sovan ^{[1
]}

Fu, Dongdong ^{[1
]}

Welstead, G. Grant ^{[1
]}

Page, David C. ^{[1
,2
,3
]}

Jaenisch, Rudolf ^{[1
,2
]}

机构：

[1] Whitehead Inst Biomed Res, Cambridge, MA 02142 USA

[2] MIT, Dept Biol, Cambridge, MA 02139 USA

[3] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

来源：

CELL STEM CELL | 2012年 / 11卷 / 03期

基金：

美国国家卫生研究院;

关键词：

EXTRACELLULAR-MATRIX COMPONENTS; STEM-CELLS; SEX DETERMINATION; SEMINIFEROUS TUBULES; MICROARRAY DATA; IN-VITRO; DIFFERENTIAL EXPRESSION; DOPAMINERGIC-NEURONS; GENE-EXPRESSION; TRANSGENIC MICE;

D O I：

10.1016/j.stem.2012.07.019

中图分类号：

Q813 [细胞工程];

学科分类号：

100113 [医学细胞生物学];

摘要：

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.

引用

页码：373 / 386

页数：14

共 44 条

[1]

Osteo-chondroprogenitor cells are derived from Sox9 expressing precursors [J].