Myc and Dnmt1 Impede the Pluripotent to Totipotent State Transition in Embryonic Stem Cells
MetadataShow full item record
CitationFu, Xudong, Wu, Xiaoji, Djekidel, Mohamed Nadhir, and Zhang, Yi. "Myc and Dnmt1 Impede the Pluripotent to Totipotent State Transition in Embryonic Stem Cells." Nature Cell Biology 21, no. 7 (2019): 835-44.
AbstractTotipotency refers to the ability of a cell to generate all the cell types of an organism. Unlike pluripotency, the establishment of totipotency is poorly understood. In mouse embryonic stem cells (mESCs), Dux drives a small percentage of cells into a totipotent state by expressing 2-cell-embyro-specific transcripts. To understand how this transition takes place, we performed single cell RNA-seq which revealed a two-step transcriptional reprogramming process characterized by downregulation of pluripotent genes in the first step and upregulation of the 2-cell embryo-specific elements in the second step. To identify factors controlling the transition, we performed a CRISPR/Cas9-mediated screen which revealed Myc and Dnmt1 as two factors preventing the transition. Mechanistic studies demonstrate that Myc prevents down-regulation of pluripotent genes in the first step, while Dnmt1 impedes 2 cell embryo-specific gene activation in the second step. Collectively, our study reveals insights into establishment and regulation of totipotent state in mESCs.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37371268
- HMS Scholarly Articles