4.6 Article

GDNF neurotrophic factor signalling determines the fate of dermal fibroblasts in wound-induced hair neogenesis and skin regeneration

Journal

EXPERIMENTAL DERMATOLOGY
Volume 31, Issue 4, Pages 577-581

Publisher

WILEY
DOI: 10.1111/exd.14526

Keywords

fibroblasts; GDNF; GFRA1; hair follicles; regeneration; RET; skin; stem cells; wound healing; wound repair

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Funding

  1. American Cancer Society [IRG-17-183-16]
  2. National Cancer Institute [1R01CA215973-01]

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The authors propose that GDNF can promote hair follicle neogenesis and skin regeneration by directing the fate of dermal fibroblasts. They plan to conduct lineage-tracing experiments and RNA sequencing experiments to study the mechanism of GDNF. This research is of great significance for advancing the fields of regenerative medicine and biology.
We propose that GDNF, a glial cell line-derived neurotrophic factor, can promote hair follicle neogenesis and skin regeneration after wounding by directing the fate of dermal fibroblasts. Our hypothesis is largely based on detailed GDNF and receptor analysis during skin regenerative stages, as well as the induction of GDNF receptors after wounding between the pro-regenerative spiny mouse (genus Acomys) and its less-regenerative descendant, the house mouse (Mus musculus). To characterize the GDNF-target cells, we will conduct a series of lineage-tracing experiments in conjunction with single-cell RNA and assay for transposase-accessible chromatin sequencing experiments. The heterogenetic dynamics of skin regeneration have yet to be fully defined, and this research will help to advance the fields of regenerative medicine and biology. Finally, we believe that stimulating the GDNF signalling pathway in fibroblasts from less-regenerative animals, such as humans, will promote skin regeneration, morphogenesis and scarless wound healing.

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