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XB-ART-61798
Science 2026 Apr 09;3926794:eadw8526. doi: 10.1126/science.adw8526.
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Species-specific oxygen sensing governs the initiation of vertebrate limb regeneration.

Tsissios G, Leleu M, Hu K, Demirtas AE, Hu H, Vinzens S, Kawanishi T, Skoufa E, Valanju A, Valente A, Noseda L, Ochi H, Herrera A, Sakar S, Tanaka M, Wickström SA, Zenk F, Aztekin C.


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Why mammals cannot regenerate limbs like amphibians do presents a long-standing puzzle in biology. To uncover the underlying differences, we compared amputation responses of embryonic mouse (Mus musculus) and Xenopus laevis 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, Xenopus 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.

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Species referenced: Xenopus laevis
Genes referenced: hif1a
GO keywords: regeneration [+]