The skin serves as a critical model for examining cellular dynamics during injury repair. The outer epidermal layer contains pilosebaceous units, including hair follicles and sebaceous glands connected to the interfollicular epidermis via the infundibulum. In a healthy state, the innermost basal epidermal cells proliferate and asymmetrically differentiate into various epidermal cell types as they ascend, contributing to the interfollicular, hair follicle, and infundibulum.
A recent study by Sarate et al. published in Cell investigates the biophysical properties of basal epidermal cells using a mouse injury model where these cells are depleted. The researchers discovered novel mechanisms linked to tissue fluidization and regeneration driven by EGFR/AP1 in the epidermis. They established an innovative injury model where basal cells in the interfollicular epidermis are ablated using diphtheria toxin in a doxycycline-dependent manner. This ablation activates and recruits neighboring and distant basal cells for epidermal regeneration.
Live imaging of individual clones in living mice showed that when more than half of the basal cells are lost, the remaining cells exhibit fluid-like behaviors. Utilizing their genetic injury model, the authors employed chromatin accessibility and transcriptome sequencing to analyze the transcriptional and epigenetic landscape associated with fluidization. Their findings indicated increased accessibility of AP1 in regenerative conditions. Furthermore, single-cell RNA sequencing suggested that Jun-Fos regulation is upregulated in regenerative cells during fluidization states.