Direct reprogramming of somatic cells is promoted by maternal transcription factor Glis1

被引：293

作者：

Maekawa, Momoko ^{[1
,2
]}

Yamaguchi, Kei ^{[3
]}

Nakamura, Tomonori ^{[1
,4
]}

Shibukawa, Ran ^{[1
,2
]}

Kodanaka, Ikumi ^{[1
,2
]}

Ichisaka, Tomoko ^{[1
,4
]}

Kawamura, Yoshifumi ^{[3
]}

Mochizuki, Hiromi ^{[3
]}

Goshima, Naoki ^{[5
]}

Yamanaka, Shinya ^{[1
,2
,4
,6
]}

机构：

[1] Kyoto Univ, Ctr iPS Cell Res & Applicat CiRA, Kyoto 6068507, Japan

[2] JST, Yamanaka iPS Cell Special Project, Kawaguchi, Saitama 3320012, Japan

[3] Japan Biol Informat Consortium, Tokyo 1350064, Japan

[4] Kyoto Univ, Inst Integrated Cell Mat Sci, Kyoto 6068507, Japan

[5] Natl Inst Adv Ind Sci & Technol, Biomed Informat Res Ctr, Tokyo 1350064, Japan

[6] Gladstone Inst Cardiovasc Dis, San Francisco, CA 94158 USA

来源：

NATURE | 2011年 / 474卷 / 7350期

关键词：

PLURIPOTENT STEM-CELLS; GENERATION; PROTEIN; MOUSE; FIBROBLASTS;

D O I：

10.1038/nature10106

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Induced pluripotent stem cells (iPSCs) are generated from somatic cells by the transgenic expression of three transcription factors collectively called OSK: Oct3/4 (also called Pou5f1), Sox2 and Klf4(1). However, the conversion to iPSCs is inefficient. The protooncogene Myc enhances the efficiency of iPSC generation by OSK but it also increases the tumorigenicity of the resulting iPSCs(2). Here we show that the Gli-like transcription factor Glis1 (Glis family zinc finger 1) markedly enhances the generation of iPSCs from both mouse and human fibroblasts when it is expressed together with OSK. Mouse iPSCs generated using this combination of transcription factors can form germline-competent chimaeras. Glis1 is enriched in unfertilized oocytes and in embryos at the one-cell stage. DNA microarray analyses show that Glis1 promotes multiple pro-reprogramming pathways, including Myc, Nanog, Lin28, Wnt, Essrb and the mesenchymal-epithelial transition. These results therefore show that Glis1 effectively promotes the direct reprogramming of somatic cells during iPSC generation.

引用

页码：225 / U268

页数：6

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