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

被引：983

作者：

Li, Ronghui ^{[1
,2
]}

Liang, Jialiang ^{[1
,2
]}

Ni, Su ^{[1
,2
]}

Zhou, Ting ^{[1
,2
]}

Qing, Xiaobing ^{[1
,2
]}

Li, Huapeng ^{[1
,2
]}

He, Wenzhi ^{[1
,2
]}

Chen, Jiekai ^{[1
,2
]}

Li, Feng ^{[1
,2
]}

Zhuang, Qiang ^{[1
,2
]}

Qin, Baoming ^{[1
,2
]}

Xu, Jianyong ^{[1
,2
]}

Li, Wen ^{[1
,2
]}

Yang, Jiayin ^{[1
,2
]}

Gan, Yi ^{[1
,2
]}

Qin, Dajiang ^{[1
,2
]}

Feng, Shipeng ^{[1
,2
]}

Song, Hong ^{[1
,2
]}

Yang, Dongshan ^{[1
,2
]}

Zhang, Biliang ^{[1
,2
]}

Zeng, Lingwen ^{[1
,2
]}

Lai, Liangxue ^{[1
,2
]}

Esteban, Miguel Angel ^{[1
,2
]}

Pei, Duanqing ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Guangzhou Inst Biomed, S China Inst Stem Cell Biol & Regenerat Med, Key Lab Regenerat Biol,Stem Cell & Canc Biol Grp, Guangzhou 510530, Guangdong, Peoples R China

[2] Chinese Acad Sci, Guangzhou Inst Hlth, S China Inst Stem Cell Biol & Regenerat Med, Key Lab Regenerat Biol,Stem Cell & Canc Biol Grp, Guangzhou 510530, Guangdong, Peoples R China

来源：

CELL STEM CELL | 2010年 / 7卷 / 01期

基金：

中国国家自然科学基金; 国家高技术研究发展计划(863计划);

关键词：

TRANSCRIPTION FACTOR SNAIL; PLURIPOTENT STEM-CELLS; HUMAN EMBRYONIC STEM; GROWTH-FACTOR-BETA; E-CADHERIN; SELF-RENEWAL; MIR-200; FAMILY; GROUND-STATE; IN-VIVO; GENERATION;

D O I：

10.1016/j.stem.2010.04.014

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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-beta 1 and TGF-beta 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.

引用

页码：51 / 63

页数：13

共 55 条

[1] Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes [J].