biostudies-literatureCarvalho SFundação para a Ciência e TecnologiaDeutsche ForschungsgemeinschaftHelmholtz AssociationHORIZON EUROPE Marie Sklodowska-Curie Actionsbio060415https://www.ebi.ac.uk/biostudies/studies/S-EPMC11070786biostudies-literatureUnknown13(4)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 eaBiology openSRRM2 splicing factor modulates cell fate in early development.PMC11070786FOX-MTN-HORIZON-MSCA - 2021-PF-01-01UIDB/04378/2020LA/P/0140/2020COVID/BD/152489/2022PD/BD/135453/201781Z0100101UIDP/04378/2020FOX-MTN-HORIZON-MSCA – 2021-PF-01-01Carvalho STang TCCKukalev APombo AMiller DStachel-Braum PGrosswendt SDiecke SCaldas PZea-Redondo LGrosso ARfalseSRRM2 splicing factor modulates cell fate in early development.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 ea2024-01-01T00:00:00Z2024 Apr2026-06-01T17:26:42.389Z2026-04-08T14:14:02.329ZS-EPMC110707863865678810.1242/bio.060415