Single-Cell RNA-Seq Reveals Dynamic Early Embryonic-like Programs during Chemical Reprogramming

Publication date: Available online 21 June 2018
Source:Cell Stem Cell
Author(s): Ting Zhao, Yao Fu, Jialiang Zhu, Yifang Liu, Qian Zhang, Zexuan Yi, Shi Chen, Zhonggang Jiao, Xiaochan Xu, Junquan Xu, Shuguang Duo, Yun Bai, Chao Tang, Cheng Li, Hongkui Deng
Chemical reprogramming provides a powerful platform for exploring the molecular dynamics that lead to pluripotency. Although previous studies have uncovered an intermediate extraembryonic endoderm (XEN)-like state during this process, the molecular underpinnings of pluripotency acquisition remain largely undefined. Here, we profile 36,199 single-cell transcriptomes at multiple time points throughout a highly efficient chemical reprogramming system using RNA-sequencing and reconstruct their progression trajectories. Through identifying sequential molecular events, we reveal that the dynamic early embryonic-like programs are key aspects of successful reprogramming from XEN-like state to pluripotency, including the concomitant transcriptomic signatures of two-cell (2C) embryonic-like and early pluripotency programs and the epigenetic signature of notable genome-wide DNA demethylation. Moreover, via enhancing the 2C-like program by fine-tuning chemical treatment, the reprogramming process is remarkably accelerated. Collectively, our findings offer a high-resolution dissection of cell fate dynamics during chemical reprogramming and shed light on mechanistic insights into the nature of induced pluripotency.

Graphical abstract

Teaser

Single-cell RNA sequencing analysis of chemical reprogramming depicts its trajectory and highlights dynamic intermediate cellular programs resembling early embryonic signatures. Zhao et al. apply these insights to develop a faster reprogramming system.


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