Single-Cell RNA-Seq Reveals Dynamic Early Embryonic-like Programs during Chemical Reprogramming
| Autor: | Junquan Xu, Chao Tang, Xiaochan Xu, Qian Zhang, Yifang Liu, Yun Bai, Shuguang Duo, Jialiang Zhu, Yao Fu, Shi Chen, Ting Zhao, Zexuan Yi, Zhonggang Jiao, Cheng Li, Hongkui Deng |
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| Rok vydání: | 2018 |
| Předmět: |
Pluripotent Stem Cells
0301 basic medicine Embryonic Development Mice Transgenic RNA-Seq Computational biology Biology Cell fate determination Transcriptome Mice 03 medical and health sciences Genetics medicine Animals Epigenetics Cells Cultured Sequence Analysis RNA Cell Biology Cellular Reprogramming Embryonic stem cell High-Throughput Screening Assays Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure DNA demethylation Molecular Medicine Single-Cell Analysis Endoderm Reprogramming |
| Zdroj: | Cell Stem Cell. 23:31-45.e7 |
| ISSN: | 1934-5909 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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