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

单细胞 RNA 测序分析揭示小鼠肝脏发育过程中的动态轨迹

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作者:Xianbin Su, Yi Shi, Xin Zou, Zhao-Ning Lu, Gangcai Xie, Jean Y H Yang, Chong-Chao Wu, Xiao-Fang Cui, Kun-Yan He, Qing Luo, Yu-Lan Qu, Na Wang, Lan Wang, Ze-Guang Han

Background

The 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.

Conclusions

Our 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.

Results

We 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. Conclusions: Our 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.

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