Induction of Pluripotency in Mouse Somatic Cells with Lineage Specifiers

被引：257

作者：

Shu, Jian ^{[1
,3
]}

Wu, Chen ^{[3
,6
]}

Wu, Yetao ^{[3
,6
]}

Li, Zhiyuan ^{[2
,7
]}

Shao, Sida ^{[1
]}

Zhao, Wenhui ^{[1
,3
]}

Tang, Xing ^{[4
]}

Yang, Huan ^{[3
,6
]}

Shen, Lijun ^{[1
]}

Zuo, Xiaohan ^{[3
,6
]}

Yang, Weifeng ^{[1
]}

Shi, Yan ^{[6
]}

Chi, Xiaochun ^{[5
]}

Zhang, Hongquan ^{[5
]}

Gao, Ge ^{[4
]}

Shu, Youmin ^{[8
]}

Yuan, Kehu ^{[8
]}

He, Weiwu ^{[8
]}

Tang, Chao ^{[2
,3
]}

Zhao, Yang ^{[1
,3
]}

Deng, Hongkui ^{[1
,3
,6
]}

机构：

[1] Peking Univ, Coll Life Sci, MOE Key Lab Cell Proliferat & Differentiat, Beijing 100871, Peoples R China

[2] Peking Univ, Ctr Quantitat Biol, Beijing 100871, Peoples R China

[3] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing 100871, Peoples R China

[4] Peking Univ, Ctr Bioinformat, State Key Lab Prot & Plant Gene Res, Coll Life Sci, Beijing 100871, Peoples R China

[5] Peking Univ, Sch Basic Med Sci, Lab Stem Cells Dev & Reprod Med, Beijing 100191, Peoples R China

[6] Peking Univ, Shenzhen Grad Sch, Sch Chem Biol & Biotechnol, Lab Chem Genom, Shenzhen 518055, Peoples R China

[7] Univ Calif San Francisco, Biophys Grad Program, San Francisco, CA 94158 USA

[8] OriGene Technol, Rockville, MD 20850 USA

来源：

CELL | 2013年 / 153卷 / 05期

基金：

美国国家科学基金会; 中国国家自然科学基金;

关键词：

EMBRYONIC STEM-CELLS; PRIMITIVE ENDODERM; DIRECT CONVERSION; HUMAN FIBROBLASTS; DIFFERENTIATION; OCT4; EXPRESSION; GENERATION; GENE; DEDIFFERENTIATION;

D O I：

10.1016/j.cell.2013.05.001

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The reprogramming factors that induce pluripotency have been identified primarily from embryonic stem cell (ESC)-enriched, pluripotency-associated factors. Here, we report that, during mouse somatic cell reprogramming, pluripotency can be induced with lineage specifiers that are pluripotency rivals to suppress ESC identity, most of which are not enriched in ESCs. We found that OCT4 and SOX2, the core regulators of pluripotency, can be replaced by lineage specifiers that are involved in mesendo-dermal (ME) specification and in ectodermal (ECT) specification, respectively. OCT4 and its substitutes attenuated the elevated expression of a group of ECT genes, whereas SOX2 and its substitutes curtailed a group of ME genes during reprogramming. Surprisingly, the two counteracting lineage specifiers can synergistically induce pluripotency in the absence of both OCT4 and SOX2. Our study suggests a "seesaw model'' in which a balance that is established using pluripotency factors and/or counteracting lineage specifiers can facilitate reprogramming.

引用

页码：963 / 975

页数：13

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