A XEN-like State Bridges Somatic Cells to Pluripotency during Chemical Reprogramming

被引：228

作者：

Zhao, Yang ^{[1
,2
]}

Zhao, Ting ^{[1
,2
,3
]}

Guan, Jingyang ^{[1
,2
]}

Zhang, Xu ^{[1
,2
]}

Fu, Yao ^{[1
,2
]}

Ye, Junqing ^{[1
,2
,4
]}

Zhu, Jialiang ^{[1
,2
]}

Meng, Gaofan ^{[1
,2
,4
]}

Ge, Jian ^{[1
,2
]}

Yang, Susu ^{[1
,2
]}

Cheng, Lin ^{[1
,2
]}

Du, Yaqin ^{[1
,2
]}

Zhao, Chaoran ^{[1
,2
]}

Wang, Ting ^{[1
,2
]}

Su, Linlin ^{[1
,2
]}

Yang, Weifeng ^{[5
]}

Deng, Hongkui ^{[1
,2
,4
]}

机构：

[1] Peking Univ, Hlth Sci Ctr, Ctr Mol & Translat Med,State Key Lab Nat & Biomim, Stem Cell Res Ctr,Sch Basic Med Sci,Dept Cell Bio, Beijing 100191, Peoples R China

[2] Peking Univ, Peking Tsinghua Ctr Life Sci, Coll Life Sci, MOE Key Lab Cell Proliferat & Differentiat, Beijing 100191, Peoples R China

[3] Peking Univ, Tsinghua Univ, Coll Life Sci, Natl Inst Biol Sci Joint Grad Program, Beijing 100871, Peoples R China

[4] Peking Univ, Shenzhen Grad Sch, Key Lab Chem Genom, Shenzhen Stem Cell Engn Lab, Shenzhen 518055, Peoples R China

[5] Beijing Vitalstar Biotechnol Co Ltd, Beijing 100012, Peoples R China

来源：

CELL | 2015年 / 163卷 / 07期

基金：

中国国家自然科学基金;

关键词：

EMBRYONIC STEM-CELLS; PRIMITIVE ENDODERM; MOUSE BLASTOCYSTS; INDUCTION; EXPRESSION; SEGREGATION; EPIBLAST; SOX17;

D O I：

10.1016/j.cell.2015.11.017

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：

Somatic cells can be reprogrammed into pluripotent stem cells (PSCs) by using pure chemicals, providing a different paradigm to study somatic reprogramming. However, the cell fate dynamics and molecular events that occur during the chemical reprogramming process remain unclear. We now show that the chemical reprogramming process requires the early formation of extra-embryonic endoderm (XEN)-like cells and a late transition from XEN-like cells to chemically- induced (Ci)PSCs, a unique route that fundamentally differs from the pathway of transcription factor-induced reprogramming. Moreover, precise manipulation of the cell fate transition in a step-wise manner through the XEN-like state allows us to identify small-molecule boosters and establish a robust chemical reprogramming system with a yield up to 1,000-fold greater than that of the previously reported protocol. These findings demonstrate that chemical reprogramming is a promising approach to manipulate cell fates.

引用

页码：1678 / 1691

页数：14

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