SRRM2 splicing factor modulates cell fate in early development

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Item Type:	Article
Title:	SRRM2 splicing factor modulates cell fate in early development
Creators Name:	Carvalho, S. and Zea-Redondo, L. and Tang, T.C.C. and Stachel-Braum, P. and Miller, D. and Caldas, P. and Kukalev, A. and Diecke, S. and Grosswendt, S. and Grosso, A.R. and Pombo, A.
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.
Keywords:	Srrm2, SRm300, SRm300Splicing, Pluripotency, Stemness, Single-Cell Transcriptomics, Animals, Mice
Source:	Biology Open
ISSN:	2046-6390
Publisher:	Company of Biologists
Volume:	13
Number:	4
Page Range:	bio060415
Date:	April 2024
Official Publication:	https://doi.org/10.1242/bio.060415
PubMed:	View item in PubMed

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