Resuscitation from Near Cell Death Unleashes Developmental Cues that Enhance Tissue Repair and Regeneration
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ABSTRACT: Resuscitation from near-cell death conditions is an intriguing but not well-understood cell biology phenomenon. First, we conclusively demonstrate that cells could revive from the early cell death phase evoked by LLOMe and other lysosomotropic agents. The resuscitation phase was found to be a highly orchestrated cellular and molecular process, where the fragmented cell organelles of the death phase fully renewed themselves within a few hours. Remarkably, the initiation of the resuscitation phase was accompanied by the upregulation of pathways of embryonic development, tissue repair, regeneration, and stemness. This was followed by the induction of networks of genes of vital cellular and metabolic pathways. Prompted by in vitro results, we tested whether LLOMe could affect tissue repair, regeneration, and stemness in vivo. Indeed, LLOMe dramatically induced repair in skin wound and corneal alkali burns mouse models. Also, it stimulated the production of hematopoietic stem/progenitor cells in the Drosophila melanogaster, enhanced tadpole tail regeneration in the frog, and promoted axon regeneration in the Caenorhabditis elegans. Fascinatingly, LLOMe treatment of frog tadpoles resulted in accelerated developmental growth. Among others, NF-ĸB signaling was found to be most critical for the revival of cells as well as the regeneration process. Thus, for the first time, we demonstrate that resuscitation from near-cell death conditions is an elegantly programmed process and that this process could be harnessed for therapeutic advances in regenerative medicine.
ORGANISM(S): Mus musculus
PROVIDER: GSE285446 | GEO | 2025/07/01
REPOSITORIES: GEO
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