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Adrenergic signaling stimulates body-wide stem cell activation for limb regeneration (2N RNA-Seq)

ABSTRACT: In axolotls, stem cells are systemically prompted to re-enter the cell cycle upon amputation. We sought to identify how the cells surrounding the systemically activated cells respond to an amputation.

ORGANISM(S): Ambystoma mexicanum

PROVIDER: GSE232082 | GEO | 2023/05/13

REPOSITORIES: GEO

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Adrenergic signaling stimulates body-wide stem cell activation for limb regeneration

Project description:In axolotls, stem cells are systemically prompted to re-enter the cell cycle upon amputation. We sought to identify whether the proliferating cells of the systemically-activated limbs are epigenetically different from those of homeostatic limbs. identify which cells drive systemic-activation response in the limbs distant to the amputation.

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Comparison of Protein Expression During Early Phases of Limb Regeneration Between Regeneration-permissive and Regeneration-deficient Axolotl

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Evi5 is required for Xenopus limb and tail regeneration

Project description:Amphibians such as the salamanders and the African clawed frog Xenopus are great models for regeneration studies because they can fully regenerate their lost organs. While axolotl can regenerate damaged organs throughout its lifetime, Xenopus has a limited regeneration capacity after metamorphosis. The ecotropic viral integrative factor 5 (Evi5), a cell-cycle-regulated protein that prevents cells from entering mitosis prematurely, is of great interest for it is highly upregulated in the limb blastema of axolotls, but its expression level remains unchanged in the fibroblastema of postmetamorphic frogs. Yet, its role in regeneration competent context in Xenopus has not been fully analyzed. Here we show that Evi5 is also upregulated in Xenopus tadpoles after limb and tail amputation, as it is in axolotls. Down-regulation of Evi5 with morpholino antisense oligos (Mo) impairs wound healing and blastema formation in limbs and tails in both axolotls and Xenopus tadpoles, suggesting a conserved function for Evi5 in regeneration. Using skin punch as a healing model we show that Evi5 is also involved in cell migration during wound healing. RNA-sequencing analysis shows that in addition to reduced signaling of Lepr, Pdgfa, Gdf5, evi5 Mo also downregulate lysine demethylases kdm6b and kdm7a, which are also required for limb regeneration. Thus, our results demonstrate that Evi5 plays a critical role in the regeneration of multiple systems in amphibians.

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