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Resolving Cell Fate Decisions during Somatic Cell Reprogramming by Single-Cell RNA-Seq. 2019
Lin Guo, and
Lihui Lin, and
Xiaoshan Wang, and
Mingwei Gao, and
Shangtao Cao, and
Yuanbang Mai, and
Fang Wu, and
Junqi Kuang, and
He Liu, and
Jiaqi Yang, and
Shilong Chu, and
Hong Song, and
Dongwei Li, and
Yujian Liu, and
Kaixin Wu, and
Jiadong Liu, and
Jinyong Wang, and
Guangjin Pan, and
Andrew P Hutchins, and
Jing Liu, and
Duanqing Pei, and
Jiekai Chen
CAS Key Laboratory of Regenerative Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, China; Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou 510530, China; Joint School of Life Sciences, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou Medical University, Guangzhou 511436, China; Guangzhou Regenerative Medicine and Health GuangDong Laboratory (GRMH-GDL), Guangzhou 510005, China.
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-γ 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.
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