Unlocking regenerative programs in mammals

lab animal Research highlights Regenerative medicine https://doi.org/10.1038/s41684-026-01735-4 Unlocking regenerative programs in mammals Check for updates Unlike terrestrial mammals, some amphibians can regenerate limbs after amputation. However, the biological basis for this difference remains elusive. A new study comparing amputated tadpole (Xenopus laevis) and embryonic mouse (Mus musculus) limbs points to oxygen sensing as a key factor underlying the divergent regenerative abilities of these two species. Using limb explants as a highly controlled ex vivo system, the researchers first showed that amputated Xenopus limbs (NF stages 53–54) readily initiated regeneration when cultured in 96-well plates. These explants rapidly closed wounds and re-established cells of the apical ectodermal ridge, a transient signaling center essential for limb development. By contrast, amputated embryonic day 12.5 mouse limbs in an air-liquid interface (ALI) culture failed to close wounds and instead showed excessive chondrogenesis. However, when cultured in 96-well plates, half of the mouse explants showed wound coverage along with reduced chondrogenesis. Suspecting that environmental oxygen levels in the different culture conditions might influence wound healing efficiency in mouse explants, the researchers measured oxygen concentrations and found that 96-well plate cultures were exposed to subatmospheric (mean 16.1 O2%) levels, while ALI cultures reached atmospheric levels (~20.9 O2%). Consistent with this observation, exposing mouse explants to 12% oxygen induced rapid wound healing in all mouse samples. Further experiments indicated that subatmospheric oxygen levels stabilized hypoxia-inducible factor 1-alpha (HIF1A), reshaped cellular biomechanical properties and promoted histone marks associated with regenerative gene activation in mouse explants compared to ALI culture conditions. Unlike mouse limbs, Xenopus limbs retained rapid wound healing even at high oxygen levels, indicating reduced oxygen sensitivity linked to lower expression of HIF1A-regulating genes. Together, these findings establish oxygen-sensing capacity as a fundamental mechanism that distinguishes regenerative from non-regenerative limbs and open new avenues for inducing limb regeneration in mammals. Alexandra Le Bras Original reference: Tsissios, G. et al. Science 392, eadw8526 (2026) Trusted and verified —by you Like atoms make up the ocean or cells make up a body, details at every level—for every article—count. Scientific Reports’ editors and reviewers pay attention to those details for each article, just like at all Nature Portfolio journals. How can you know? By how many researchers like you publish, read, and cite Scientific Reports every day. Scientific Reports. Your hub for global research. nature.com/srep Lab Animal | Volume 55 | May 2026 | 160 160  (...truncated)