| Literature DB >> 30772174 |
Lin Guo1, Lihui Lin2, Xiaoshan Wang2, Mingwei Gao2, Shangtao Cao2, Yuanbang Mai3, Fang Wu2, Junqi Kuang2, He Liu2, Jiaqi Yang3, Shilong Chu3, Hong Song3, Dongwei Li2, Yujian Liu4, Kaixin Wu2, Jiadong Liu2, Jinyong Wang2, Guangjin Pan2, Andrew P Hutchins3, Jing Liu3, Duanqing Pei5, Jiekai Chen6.
Abstract
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.Entities:
Keywords: Dppa5a; Interferon gamma; Klf4; Oct4; Sox2; bifurcation; cell fate decision; induced pluripotent stem cells; reprogramming; single-cell RNA sequencing
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Year: 2019 PMID： 30772174 DOI： 10.1016/j.molcel.2019.01.042
Source DB: PubMed Journal: Mol Cell ISSN： 1097-2765 Impact factor: 17.970