Functional Genomics Reveals a BMP-Driven Mesenchymal-to-Epithelial Transition in the Initiation of Somatic Cell Reprogramming

被引：824

作者：

Samavarchi-Tehrani, Payman ^{[1
,3
]}

Golipour, Azadeh ^{[1
,3
]}

David, Laurent ^{[1
]}

Sung, Hoon-Ki ^{[2
]}

Beyer, Tobias A. ^{[1
]}

Datti, Alessandro ^{[1
]}

Woltjen, Knut ^{[2
]}

Nagy, Andras ^{[2
,3
]}

Wrana, Jeffrey L. ^{[1
,3
]}

机构：

[1] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Syst Biol, Toronto, ON M5G 1X5, Canada

[2] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Ctr Stem Cells & Tissue Engn, Toronto, ON M5G 1X5, Canada

[3] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada

来源：

CELL STEM CELL | 2010年 / 7卷 / 01期

基金：

美国国家科学基金会;

关键词：

PLURIPOTENT STEM-CELLS; MIR-200; FAMILY; NANOG; FIBROBLASTS; EXPRESSION; DIFFERENTIATION; GENERATION; SALL4; INDUCTION; SYSTEM;

D O I：

10.1016/j.stem.2010.04.015

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Somatic cells can be reprogrammed to induced pluripotent stem cells (iPSCs) by expression of defined embryonic factors. However, little is known of the molecular mechanisms underlying the reprogramming process. Here we explore somatic cell reprogramming by exploiting a secondary mouse embryonic fibroblast model that forms iPSCs with high efficiency upon inducible expression of Oct4, Klf4, c-Myc, and Sox2. Temporal analysis of gene expression revealed that reprogramming is a multistep process that is characterized by initiation, maturation, and stabilization phases. Functional analysis by systematic RNAi screening further uncovered a key role for BMP signaling and the induction of mesenchymal-to-epithelial transition (MET) during the initiation phase. We show that this is linked to BMP-dependent induction of miR-205 and the miR-200 family of microRNAs that are key regulators of MET. These studies thus define a multistep mechanism that incorporates a BMP-miRNA-MET axis during somatic cell reprogramming.

引用

页码：64 / 77

页数：14

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