PRRX1 is a key regulator in the phenotypic transition between human normal dermal and keloid fibroblasts

Abstract

Background

Scarring after skin trauma is a major clinical challenge, as it affects patients’ appearance and function.

Objective

Given that human foetal skin possesses scarless wound healing ability, we aimed to understand the differences among human foetal skin, postnatal skin, and keloid tissue to find out the key factors affecting wound healing outcome.

Methods

We used spatial transcriptomics (ST), histological imaging, and other methods to investigate the cellular and molecular characteristics underlying scarless healing by comparing these skin types.

Results

We identified histological and cellular differences among these samples, including the extracellular matrix, hair follicles, stem cells, and immune cells. Significant heterogeneity was found in fibroblasts across all samples. Among these fibroblast subpopulations, the proportion of paired related homeobox 1 (PRRX1)-positive fibroblast increased from foetus to postnatal skin (PS) and further in keloids. We validated PRRX1’s roles in regulating the phenotypic transition between normal and keloid fibroblasts. A three-dimensional human keloid model was used to further confirm its roles at the tissue level.

Conclusions

In summary, our work explores the unique characteristics of foetal skin and identifies an important transcription factor in regulating scarless healing, which provides the translational potential for future clinical treatments aimed at promoting scarless wound healing.