Single-cell RNA-Seq analysis reveals dynamic trajectories during mouse liver development

BMC Genomics

Research Article

Gangcai Xie¹  Zhao-Ning Lu²  Xin Zou²  Chong-Chao Wu²  Kun-Yan He²  Lan Wang²  Xianbin Su²  Qing Luo²  Yu-Lan Qu²  Yi Shi²  Xiao-Fang Cui²  Na Wang²  Ze-Guang Han³  Jean Y. H. Yang⁴ 

[1] Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, 320 Yueyang Road, Shanghai, China;Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, China;Key Laboratory of Systems Biomedicine (Ministry of Education) and Collaborative Innovation Center of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, China;Shanghai-MOST Key Laboratory for Disease and Health Genomics, Chinese National Human Genome Center at Shanghai, Shanghai, China;School of Mathematics and Statistics, The University of Sydney, Sydney, Australia;

关键词: Liver stem/progenitor cells;    Single-cell RNA-Seq;    Developmental trajectory;    Cholangiocyte;    Fate decision;   

DOI  :  10.1186/s12864-017-4342-x

 received in 2017-09-07, accepted in 2017-11-21,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe differentiation and maturation trajectories of fetal liver stem/progenitor cells (LSPCs) are not fully understood at single-cell resolution, and a priori knowledge of limited biomarkers could restrict trajectory tracking.ResultsWe employed marker-free single-cell RNA-Seq to characterize comprehensive transcriptional profiles of 507 cells randomly selected from seven stages between embryonic day 11.5 and postnatal day 2.5 during mouse liver development, and also 52 Epcam-positive cholangiocytes from postnatal day 3.25 mouse livers. LSPCs in developing mouse livers were identified via marker-free transcriptomic profiling. Single-cell resolution dynamic developmental trajectories of LSPCs exhibited contiguous but discrete genetic control through transcription factors and signaling pathways. The gene expression profiles of cholangiocytes were more close to that of embryonic day 11.5 rather than other later staged LSPCs, cuing the fate decision stage of LSPCs. Our marker-free approach also allows systematic assessment and prediction of isolation biomarkers for LSPCs.ConclusionsOur data provide not only a valuable resource but also novel insights into the fate decision and transcriptional control of self-renewal, differentiation and maturation of LSPCs.

【 授权许可】

CC BY   
© The Author(s). 2017