| RRC ID |
88288
|
| Author |
Zhao T, Fu Y, Zhu J, Liu Y, Zhang Q, Yi Z, Chen S, Jiao Z, Xu X, Xu J, Duo S, Bai Y, Tang C, Li C, Deng H.
|
| Title |
Single-Cell RNA-Seq Reveals Dynamic Early Embryonic-like Programs during Chemical Reprogramming.
|
| Journal |
Cell Stem Cell
|
| Abstract |
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.
|
| Volume |
23(1)
|
| Pages |
31-45.e7
|
| Published |
2018-7-5
|
| DOI |
10.1016/j.stem.2018.05.025
|
| PII |
S1934-5909(18)30280-7
|
| PMID |
29937202
|
| MeSH |
Animals
Cells, Cultured
Cellular Reprogramming / drug effects*
Embryonic Development / drug effects
Embryonic Development / genetics*
High-Throughput Screening Assays
Mice
Mice, Inbred C57BL
Mice, Transgenic
Pluripotent Stem Cells / cytology*
Pluripotent Stem Cells / drug effects*
Sequence Analysis, RNA*
Single-Cell Analysis*
Transcriptome
|
| IF |
20.86
|
| Resource |
| Mice |
RBRC00771 |
