biostudies-literatureUnknown29(1)Fang YPluripotency, the ability of cells to self-renew and differentiate into all body lineages, is vital for mammalian early development. This study presented a comprehensive comparative transcriptomic analysis of embryonic stem cells across multiple mammalian species, defining their progression through expanded/extended, naive, formative, and primed pluripotency states. Our findings revealed both conserved and species-specific mechanisms underlying pluripotency regulation. We also emphasized the limitations of existing state-specific markers and their limited cross-species applicability, while identifying <i>de novo</i> pluripotency markers. Despite variability in gene expression dynamics, gene co-expression networks showed remarkable conservation across species. Among pluripotency states, theiScience114542https://www.ebi.ac.uk/biostudies/studies/S-EPMC12828385biostudies-literatureComparative transcriptomic analysis of embryonic stem cells across mammalian species.PMC12828385Li GBiga PRShi MZhang JDuan JEWilkinson GSTian XCLarschan ERandolph ECFang YIISAGE ConsortiumBronikowski AMMeisel RGamble TSingh RSu YWalters JRWebb AYu XTang YRiddle NCfalseComparative transcriptomic analysis of embryonic stem cells across mammalian species.Pluripotency, the ability of cells to self-renew and differentiate into all body lineages, is vital for mammalian early development. This study presented a comprehensive comparative transcriptomic analysis of embryonic stem cells across multiple mammalian species, defining their progression through expanded/extended, naive, formative, and primed pluripotency states. Our findings revealed both conserved and species-specific mechanisms underlying pluripotency regulation. We also emphasized the limitations of existing state-specific markers and their limited cross-species applicability, while identifying <i>de novo</i> pluripotency markers. Despite variability in gene expression dynamics, gene co-expression networks showed remarkable conservation across species. Among pluripotency states, the2026-01-01T00:00:00Z2026 Jan2026-06-21T04:45:32.099Z2026-06-21T03:07:33.551ZS-EPMC128283854158356210.1016/j.isci.2025.114542