Myc and Dnmt1 impede the pluripotent to totipotent state transition in embryonic stem cells
| Autor: | Yi Zhang, Xudong Fu, Xiaoji Wu, Mohamed Nadhir Djekidel |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
Pluripotent Stem Cells Cell type Cell Genes myc Biology Article Epigenesis Genetic 03 medical and health sciences Mice 0302 clinical medicine Downregulation and upregulation medicine Animals Embryonic Stem Cells 030304 developmental biology Epigenesis Regulation of gene expression 0303 health sciences Totipotent Cell Differentiation Mouse Embryonic Stem Cells Cell Biology Cellular Reprogramming Embryonic stem cell Cell biology medicine.anatomical_structure 030220 oncology & carcinogenesis Reprogramming Totipotent Stem Cells |
| Zdroj: | Nature cell biology. 21(7) |
| ISSN: | 1476-4679 |
| Popis: | Totipotency refers to the ability of a cell to generate all of the cell types of an organism. Unlike pluripotency, the establishment of totipotency is poorly understood. In mouse embryonic stem cells, Dux drives a small percentage of cells into a totipotent state by expressing 2-cell-embryo-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 downregulation of pluripotent genes in the first step, while Dnmt1 impedes 2-cell-embryo-specific gene activation in the second step. Collectively, the findings of our study reveal insights into the establishment and regulation of the totipotent state in mouse embryonic stem cells. |
| Databáze: | OpenAIRE |
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