GEOGenomics Mus musculusXenopus laevisGenome binding/occupancy profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE292734GEOGSEfalseSpecies-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.2026/04/09GSE292734GSM8864492GSM8864493GSM8864490GSM8864491GSM8864456GSM8864457GSM8864498GSM8864499GSM8864496GSM8864497GSM8864494GSM8864495GSM8864458GSM8864459GSM8864460GSM8864467GSM8864500GSM8864501GSM8864468GSM8864465GSM8864466GSM8864463GSM8864464GSM8864461GSM8864462GSM8864508GSM8864509GSM8864506GSM8864507GSM8864504GSM8864505GSM8864502GSM8864469GSM8864503GSM8864470GSM8864471GSM8864478GSM8864511GSM8864479GSM8864512GSM8864476GSM8864510GSM8864477GSM8864474GSM8864475GSM8864472GSM8864473GSM8864481GSM8864482GSM8864480GSM8864489GSM8864487GSM8864488GSM8864485GSM8864486GSM8864483GSM88644843447534551292734 Mus musculusXenopus laevis[41955383]