Chromatin Accessibility Dynamics during Chemical Induction of Pluripotency

被引：91

作者：

Cao, Shangtao ^{[1
,2
,4
]}

Yu, Shengyong ^{[1
,2
]}

Li, Dongwei ^{[1
,2
]}

Ye, Jing ^{[1
,2
]}

Yang, Xuejie ^{[1
,2
,4
]}

Li, Chen ^{[1
,2
,4
]}

Wang, Xiaoshan ^{[1
,2
,3
,4
]}

Mai, Yuanbang ^{[1
,2
]}

Qin, Yue ^{[1
,2
,4
]}

Wu, Jian ^{[1
,2
,4
]}

He, Jiangping ^{[1
,2
,4
]}

Zhou, Chunhua ^{[1
,2
,4
]}

Liu, He ^{[1
,2
,4
]}

Zhao, Bentian ^{[1
,2
]}

Shu, Xiaodong ^{[1
,2
,3
]}

Wu, Chuman ^{[1
,2
]}

Chen, Ruiping ^{[5
]}

Chan, Waiyee ^{[6
]}

Pan, Guangjin ^{[1
,2
,3
]}

Chen, Jiekai ^{[1
,2
,3
,6
,7
]}

Liu, Jing ^{[1
,2
,6
,7
]}

Pei, Duanqing ^{[1
,2
,3
,6
,7
]}

机构：

[1] Chinese Acad Sci, South China Inst Stem Cell Biol & Regenerat Med, Guangzhou Inst Biomed & Hlth, CAS Key Lab Regenerat Biol, Guangzhou 510530, Guangdong, Peoples R China

[2] Chinese Acad Sci, South China Inst Stem Cell Biol & Regenerat Med, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Stem Cell & Regenerat Med, Guangzhou 510530, Guangdong, Peoples R China

[3] Chinese Acad Sci, Supercomp Ctr, Guangzhou Branch, Guangzhou 510530, Guangdong, Peoples R China

[4] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[5] South China Univ Technol, Sch Med, Guangzhou 510006, Guangdong, Peoples R China

[6] Chinese Univ Hong Kong, CUHK GIBH Joint Lab Stem Cell & Regenerat Med, Shatin, Hong Kong, Peoples R China

[7] GUANGZHOU Regenerat Med & Hlth Guangdong Lab GIBH, Guangzhou 510530, Guangdong, Peoples R China

来源：

CELL STEM CELL | 2018年 / 22卷 / 04期

基金：

中国国家自然科学基金; 国家重点研发计划;

关键词：

STEM-CELLS; SOMATIC-CELLS; MOUSE FIBROBLASTS; GROUND-STATE; GENERATION; OCT4; VIRUS; KLF4;

D O I：

10.1016/j.stem.2018.03.005

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

Despite its exciting potential, chemical induction of pluripotency (CIP) efficiency remains low and the mechanisms are poorly understood. We report the development of an efficient two-step serum-and replating-free CIP protocol and the associated chromatin accessibility dynamics (CAD) by assay for transposase-accessible chromatin (ATAC)-seq. CIP reorganizes the somatic genome to an intermediate state that is resolved under 2iL condition by reclosing previously opened loci prior to pluripotency acquisition with gradual opening of loci enriched with motifs for the OCT/SOX/KLF families. Bromodeoxyuridine, a critical ingredient of CIP, is responsible for both closing and opening critical loci, at least in part by preventing the opening of loci enriched with motifs for the AP1 family and facilitating the opening of loci enriched with SOX/KLF/GATA motifs. These changes differ markedly from CAD observed during Yamanaka-factor-driven reprogramming. Our study provides insights into small-molecule-based reprogramming mechanisms and reorganization of nuclear architecture associated with cell-fate decisions.

引用

页码：529 / +

页数：19

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