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

作者：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.; Liu, Jing; Pei, Duanqing; Chen, Jiekai

来源：Molecular Cell, 2019, 73(4): 815-+.

DOI：10.1016/j.molcel.2019.01.042

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

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.

• 出版日期2019-2-21
• 单位中国科学技术大学; 广州医科大学; 中国科学院; 中国科学院广州生物医药与健康研究院; 香港中文大学; 中国科学院大学