biostudies-literatureByers CEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNICHD NIH HHSNIA NIH HHSNIH Office of the DirectorNCI NIH HHSNational Institute of General Medical SciencesNIGMS NIH HHSNIH HHSe109445https://www.ebi.ac.uk/biostudies/studies/S-EPMC8762565biostudies-literatureUnknown41(2)Genetically diverse pluripotent stem cells display varied, heritable responses to differentiation cues. Here, we harnessed these disparities through derivation of mouse embryonic stem cells from the BXD genetic reference panel, along with C57BL/6J (B6) and DBA/2J (D2) parental strains, to identify loci regulating cell state transitions. Upon transition to formative pluripotency, B6 stem cells quickly dissolved naïve networks adopting gene expression modules indicative of neuroectoderm lineages, whereas D2 retained aspects of naïve pluripotency. Spontaneous formation of embryoid bodies identified divergent differentiation where B6 showed a propensity toward neuroectoderm and D2 toward definitive endoderm. Genetic mapping identified major trans-acting loci co-regulating chromatin accessibiliThe EMBO journalGenetic control of the pluripotency epigenome determines differentiation bias in mouse embryonic stem cells.PMC8762565R35 GM133495T32 HD007065R35GM133724P30 CA034196R35 GM133724P40OD011102T32HD007065T32 AG062409P40 OD011102Munger SCBaker CLSpruce CReinholdt LGSkelly DAByers CFortin HJHartig EICzechanski AfalseGenetic control of the pluripotency epigenome determines differentiation bias in mouse embryonic stem cells.Genetically diverse pluripotent stem cells display varied, heritable responses to differentiation cues. Here, we harnessed these disparities through derivation of mouse embryonic stem cells from the BXD genetic reference panel, along with C57BL/6J (B6) and DBA/2J (D2) parental strains, to identify loci regulating cell state transitions. Upon transition to formative pluripotency, B6 stem cells quickly dissolved naïve networks adopting gene expression modules indicative of neuroectoderm lineages, whereas D2 retained aspects of naïve pluripotency. Spontaneous formation of embryoid bodies identified divergent differentiation where B6 showed a propensity toward neuroectoderm and D2 toward definitive endoderm. Genetic mapping identified major trans-acting loci co-regulating chromatin accessibili2022-01-01T00:00:00Z2022 Dec2026-05-09T22:39:06.102Z2025-04-07T03:16:06.224ZS-EPMC87625653493132310.15252/embj.2021109445