SRRM2 splicing factor modulates cell fate in early development.
Biol Open
; 13(4)2024 Apr 15.
Article
em En
| MEDLINE
| ID: mdl-38656788
ABSTRACT
Embryo development is an orchestrated process that relies on tight regulation of gene expression to guide cell differentiation and fate decisions. The Srrm2 splicing factor has recently been implicated in developmental disorders and diseases, but its role in early mammalian development remains unexplored. Here, we show that Srrm2 dosage is critical for maintaining embryonic stem cell pluripotency and cell identity. Srrm2 heterozygosity promotes loss of stemness, characterised by the coexistence of cells expressing naive and formative pluripotency markers, together with extensive changes in gene expression, including genes regulated by serum-response transcription factor (SRF) and differentiation-related genes. Depletion of Srrm2 by RNA interference in embryonic stem cells shows that the earliest effects of Srrm2 heterozygosity are specific alternative splicing events on a small number of genes, followed by expression changes in metabolism and differentiation-related genes. Our findings unveil molecular and cellular roles of Srrm2 in stemness and lineage commitment, shedding light on the roles of splicing regulators in early embryogenesis, developmental diseases and tumorigenesis.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Diferenciação Celular
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Regulação da Expressão Gênica no Desenvolvimento
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Desenvolvimento Embrionário
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Biol Open
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Alemanha