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

72 Pages Posted: 13 Apr 2018 Sneak Peek Status: Review Complete

See all articles by Lin Guo

Lin Guo

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Xiaoshan Wang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Lihui Lin

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Mingwei Gao

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Junqi Kuang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Yuanbang Mai

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Fang Wu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

He Liu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Jiaqi Yang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Shilong Chu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Hong Song

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Yujian Liu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Jiadong Liu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Jinyong Wang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangjin Pan

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Andrew P. Hutchins

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Jing Liu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Jiekai Chen

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Duanqing Pei

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

More...

Abstract

Cell makes fate decision with intrinsic and extrinsic cues. It has been difficult to define the precise decision process due to cellular heterogeneity. Here we map the cell fate continuum generated during somatic reprogramming by Oct4, Sox2 and Klf4 at single cell resolution. We show that the reprogramming cells initially march through mesenchyme-epithelial transition, then bifurcate into non-reprogramming (NR) and reprogramming (R) fates. The R cells continue to acquire Oct4 activation and then bifurcate again into Dppa5a chimera competent and Dppa5a- chimera incompetent cells. Mechanistically, we show that the NR/R bifurcation is controlled by Klf4 and Sox2 and the final Dppa5a rate-limiting step in part by IFN-γ, a cytokine activated during reprogramming. Our study identifies two previously unknown cell fate checkpoints along the reprogramming pathway, highlighting single-cell analysis as a tool to understand cell fate decisions.

Keywords: reprogramming; induced pluripotent stem cells; single-cell RNA sequencing (RNA-seq); bifurcation; cell fate decision

Suggested Citation

Guo, Lin and Wang, Xiaoshan and Lin, Lihui and Gao, Mingwei and Kuang, Junqi and Mai, Yuanbang and Wu, Fang and Liu, He and Yang, Jiaqi and Chu, Shilong and Song, Hong and Liu, Yujian and Liu, Jiadong and Wang, Jinyong and Pan, Guangjin and Hutchins, Andrew P. and Liu, Jing and Chen, Jiekai and Pei, Duanqing, Resolving Cell Fate Decisions During Somatic Cell Reprogramming by Single-Cell RNA-Seq (2018). Available at SSRN: https://ssrn.com/abstract=3155787 or http://dx.doi.org/10.2139/ssrn.3155787
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Lin Guo

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Xiaoshan Wang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Lihui Lin

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Mingwei Gao

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Junqi Kuang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Yuanbang Mai

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Fang Wu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

He Liu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Jiaqi Yang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Shilong Chu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Hong Song

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Yujian Liu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Jiadong Liu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Jinyong Wang

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Guangjin Pan

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Andrew P. Hutchins

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Jing Liu

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Jiekai Chen

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

Duanqing Pei (Contact Author)

Chinese Academy of Sciences (CAS) - Key Laboratory of Regenerative Biology

Guangzhou, 510530
China

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