1. Resolving Cell Fate Decisions during Somatic Cell Reprogramming by Single-Cell RNA-Seq.
- Author
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Guo, Lin, Lin, Lihui, Wang, Xiaoshan, Gao, Mingwei, Cao, Shangtao, Mai, Yuanbang, Wu, Fang, Kuang, Junqi, Liu, He, Yang, Jiaqi, Chu, Shilong, Song, Hong, Li, Dongwei, Liu, Yujian, Wu, Kaixin, Liu, Jiadong, Wang, Jinyong, Pan, Guangjin, Hutchins, Andrew P., and Liu, Jing
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SOMATIC cells , *INDUCED pluripotent stem cells , *RNA sequencing , *CELL determination , *HETEROGENEOUS computing - Abstract
Summary 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. Graphical Abstract Highlights • Cell fate continuum generated by somatic reprogramming • Single-cell Orientation Tracing (SOT) for fate trajectory detection • Two non-reprogramming trajectories regulated by Klf4 and IFN-γ • A generic bifurcation model for cell fate decisions Guo et al. report the cell fate continuum during induced pluripotent stem cell (iPSC) reprogramming at single-cell resolution. By developing SOT as a new analytic tool, they identify several previously unknown bifurcation points along the reprogramming path and propose a generic bifurcation model for cell fate decisions. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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