A Mesenchymal-to-Epithelial Transition Initiates and Is Required for the Nuclear Reprogramming of Mouse Fibroblasts

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• 作者：Ronghui Li ; Jialiang Liang ; Su Ni ; Ting Zhou ; Xiaobing Qing ; Huapeng Li ; Wenzhi He ; Jiekai Chen ; Feng Li ; Qiang Zhuang ; Baoming Qin ; Jianyong Xu ; Wen Li ; Jiayin Yang ; Yi Gan ; Dajiang Qin ; Shipeng Feng
• 刊名：Cell Stem Cell
• 出版年：2010
• 出版时间：2 July 2010
• 年：2010
• 卷：7
• 期：1
• 页码：51-63
• 全文大小：1590 K

文摘

Summary

Epithelial-to-mesenchymal transition (EMT) is a developmental process important for cell fate determination. Fibroblasts, a product of EMT, can be reset into induced pluripotent stem cells (iPSCs) via exogenous transcription factors but the underlying mechanism is unclear. Here we show that the generation of iPSCs from mouse fibroblasts requires a mesenchymal-to-epithelial transition (MET) orchestrated by suppressing pro-EMT signals from the culture medium and activating an epithelial program inside the cells. At the transcriptional level, Sox2/Oct4 suppress the EMT mediator Snail, c-Myc downregulates TGF-β1 and TGF-β receptor 2, and Klf4 induces epithelial genes including E-cadherin. Blocking MET impairs the reprogramming of fibroblasts whereas preventing EMT in epithelial cells cultured with serum can produce iPSCs without Klf4 and c-Myc. Our work not only establishes MET as a key cellular mechanism toward induced pluripotency, but also demonstrates iPSC generation as a cooperative process between the defined factors and the extracellular milieu.

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