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

Quan M Phan,Gerardo G Herrera,Lucia Salz,Gracelyn M Fine,Ben Wildman,Iwona M Driskell,Ryan R Driskell

doi:10.7554/elife.60066

Abstract

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.

Highlights

We have previously shown that papillary fibroblasts are the primary source of de-novo dermal papilla during skin development, which are required for hair formation (Driskell et al, 2013)
Our work has identified Lef[1], as the factor in fibroblast of developing skin, that can transform adult tissue to regenerate without harmful phenotypes
Consisted of 56.5% cells from the Developing condition and 37.1% cells from the Regenerating condition. These results indicate that there is a distinct separation between fibroblast sub-types that support regeneration or scarring based on conditions

Summary

Objectives

Since our goal was to identify a cell type that uniquely represented the ability to support hair follicle regeneration in wounds, we focused on cluster 0 which are papillary fibroblasts represented by the Regenerating condition

Methods

Findings

Discussion

Conclusion