GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE314nnn/GSE314013/primaryOK200GenomicsMus musculusGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314013GEOGSEfalseSpecies-specific oxygen sensing governs the initiation of vertebrate limb regenerationWhy mammals cannot regenerate limbs, unlike amphibians, presents a longstanding puzzle in biology. We show that exposing ex vivo amputated embryonic mouse limbs to subatmospheric oxygen environment, or stabilizing oxygen-sensitive HIF1A enables not only rapid wound healing, but alters cellular mechanics, and reshapes the histone landscape to prime regenerative fates. Conversely, regenerative Xenopus tadpole limbs display low oxygen-sensing capacity, robust wound healing, a regenerative histone landscape, and glycolytic programs even under high oxygen. This reduced oxygen-sensing capacity, in stark contrast to mammals, associates with decreased HIF1A-regulating gene expressions. Our findings thus uncover species-specific oxygen sensing as a unifying mechanism for limb regeneration initiation across vertebrates, reveal how aquatic subatmospheric habitats may enhance regenerative capabilities, and identify targetable barriers to unlock latent limb regenerative programs in adult mammals.2026/05/04GSE314013GSM9379893GSM9379892GSM9379894GSM9379891GSM9379890GSM937988934290314013Mus musculus[41955383]