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To uncover the underlying differences, we compared amputation responses of embryonic mouse (\n                    <jats:italic toggle=\"yes\">Mus musculus<\/jats:italic>\n                    ) and\n                    <jats:italic toggle=\"yes\">Xenopus laevis<\/jats:italic>\n                    tadpole limbs. Lowering environmental oxygen or stabilizing the oxygen-sensitive hypoxia-inducible factor 1A (HIF1A) induced rapid wound healing in mouse limbs. This response was accompanied by altered cellular mechanics, metabolism, and a histone landscape that primed regenerative cell states. Conversely,\n                    <jats:italic toggle=\"yes\">Xenopus<\/jats:italic>\n                    tadpole limbs retained these features even under high oxygen levels. Their reduced oxygen-sensing capacity was associated with decreased HIF1A-regulating gene expression. Our results thus identify species-specific oxygen-sensing capacity as a fundamental, targetable mechanism that can unlock latent regenerative programs in mammals.\n                  <\/jats:p>","DOI":"10.1126\/science.adw8526","type":"journal-article","created":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T18:02:54Z","timestamp":1775757774000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":12,"title":["Species-specific oxygen sensing governs the initiation of vertebrate limb regeneration"],"prefix":"10.1126","volume":"392","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5219-616X","authenticated-orcid":true,"given":"Georgios","family":"Tsissios","sequence":"first","affiliation":[{"name":"School of Life Sciences, EPFL, Lausanne, Switzerland."},{"name":"Friedrich Miescher Laboratory of the Max Planck Society (FML), T\u00fcbingen, 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