Resolving Cell Fate Decisions during Somatic Cell Reprogramming by Single-Cell RNA-Seq

被引：64

作者：

Guo, Lin ^{[1
,2
,3
,5
]}

Lin, Lihui ^{[1
,2
,4
]}

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

Gao, Mingwei ^{[1
,2
,4
]}

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

Mai, Yuanbang ^{[1
,2
]}

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

Kuang, Junqi ^{[1
,2
,4
]}

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

Yang, Jiaqi ^{[1
,2
]}

Chu, Shilong ^{[1
,2
]}

Song, Hong ^{[1
,2
]}

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

Liu, Yujian ^{[1
,2
,3
]}

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

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

Wang, Jinyong ^{[1
,2
,4
]}

Pan, Guangjin ^{[1
,2
,4
]}

Hutchins, Andrew P. ^{[1
,2
,7
]}

Liu, Jing ^{[1
,2
]}

Pei, Duanqing ^{[1
,2
,3
,4
,5
,6
]}

Chen, Jiekai ^{[1
,2
,3
,4
,5
]}

机构：

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

[2] Guangdong Prov Key Lab Stem Cell & Regenerat Med, Guangzhou 510530, Guangdong, Peoples R China

[3] Guangzhou Med Univ, Joint Sch Life Sci, Guangzhou Inst Biomed & Hlth, Chinese Acad Sci, Guangzhou 511436, Guangdong, Peoples R China

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

[5] Guangzhou Regenerat Med & Hlth GuangDong Lab, Guangzhou 510005, Guangdong, Peoples R China

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

[7] Univ Sci & Technol China, Dept Biol, Shenzhen 518055, Peoples R China

来源：

MOLECULAR CELL | 2019年 / 73卷 / 04期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

PLURIPOTENT STEM-CELLS; CHROMATIN ACCESSIBILITY DYNAMICS; MOLECULAR ROADMAP; INNATE IMMUNITY; EXPRESSION; FIBROBLASTS; STATE; KLF4; EFFICIENCY; INDUCTION;

D O I：

10.1016/j.molcel.2019.01.042

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 induced pluripotent stem cells (iPSCs), which is a highly heterogeneous process. Here we report the cell fate continuum during somatic cell reprogramming at single-cell resolution. We first develop SOT to analyze cell fate continuum from Oct4/Sox2/Klf4- or OSK-mediated reprogramming and show that cells bifurcate into two categories, reprogramming potential (RP) or non-reprogramming (NR). We further show that Klf4 contributes to Cd34+/Fxyd5+/Psca+ keratinocyte-like NR fate and that IFN-gamma impedes the final transition to chimera-competent pluripotency along the RP cells. We analyze more than 150,000 single cells from both OSK and chemical reprograming and identify additional NR/RP bifurcation points. Our work reveals a generic bifurcation model for cell fate decisions during somatic cell reprogramming that may be applicable to other systems and inspire further improvements for reprogramming.

引用

页码：815 / +

页数：22

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