Lef1 expression in fibroblasts maintains developmental potential in adult skin to regenerate wounds

Scars are a serious health concern for burn victims and individuals with skin conditions associated with wound healing. Here, we identify regenerative factors in neonatal murine skin that transforms adult skin to regenerate instead of only repairing wounds with a scar, without perturbing development...

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Bibliographic Details
Published in:eLife 2020-09, Vol.9
Main Authors: Phan, Quan M, Fine, Gracelyn M, Salz, Lucia, Herrera, Gerardo G, Wildman, Ben, Driskell, Iwona M, Driskell, Ryan R
Format: Article
Language:English
Subjects:
Animals
Cells, Cultured
dermal papilla
Female
fibroblast heterogeneity
Fibroblasts - metabolism
Lef1
Lymphoid Enhancer-Binding Factor 1 - metabolism
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
regeneration
Skin
Skin - cytology
Skin - metabolism
Skin diseases
Stem Cells and Regenerative Medicine
Transcription (Genetics)
wound healing
Wound Healing - physiology
Wounds
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Summary:Scars are a serious health concern for burn victims and individuals with skin conditions associated with wound healing. Here, we identify regenerative factors in neonatal murine skin that transforms adult skin to regenerate instead of only repairing wounds with a scar, without perturbing development and homeostasis. Using scRNA-seq to probe unsorted cells from regenerating, scarring, homeostatic, and developing skin, we identified neonatal papillary fibroblasts that form a transient regenerative cell type that promotes healthy skin regeneration in young skin. These fibroblasts are defined by the expression of a canonical Wnt transcription factor Lef1 and using gain- and loss of function genetic mouse models, we demonstrate that Lef1 expression in fibroblasts primes the adult skin macroenvironment to enhance skin repair, including regeneration of hair follicles with arrector pili muscles in healed wounds. Finally, we share our genomic data in an interactive, searchable companion website (https://skinregeneration.org/). Together, these data and resources provide a platform to leverage the regenerative abilities of neonatal skin to develop clinically tractable solutions that promote the regeneration of adult tissue.
ISSN:2050-084X
2050-084X
DOI:10.7554/elife.60066