Maternal factor NELFA drives a 2C-like state in mouse embryonic stem cells.
Nat Cell Biol
; 22(2): 175-186, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31932739
ABSTRACT
Mouse embryonic stem cells (ESCs) sporadically transit into an early embryonic-like state characterized by the expression of 2-cell (2C) stage-restricted transcripts. Here, we identify a maternal factor-negative elongation factor A (NELFA)-whose heterogeneous expression in mouse ESCs is coupled to 2C gene upregulation and expanded developmental potential in vivo. We show that NELFA partners with Top2a in an interaction specific to the 2C-like state, and that it drives the expression of Dux-a key 2C regulator. Accordingly, loss of NELFA and/or Top2a suppressed Dux activation. Further characterization of 2C-like cells uncovered reduced glycolytic activity; remarkably, mere chemical suppression of glycolysis was sufficient to promote a 2C-like fate, obviating the need for genetic manipulation. Global chromatin state analysis on NELFA-induced cells revealed decommissioning of ESC-specific enhancers, suggesting ESC-state impediments to 2C reversion. Our study positions NELFA as one of the earliest drivers of the 2C-like state and illuminates factors and processes that govern this transition.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Regulação da Expressão Gênica no Desenvolvimento
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Desenvolvimento Embrionário
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Células-Tronco Embrionárias Murinas
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Nat Cell Biol
Ano de publicação:
2020
Tipo de documento:
Article