Defining epidermal basal cell states during skin homeostasis and wound healing using single-cell transcriptomics

Abstract

Our knowledge of transcriptional heterogeneities in epithelial stem/progenitor cell compartments is limited. Epidermal basal cells sustain cutaneous tissue maintenance and drive wound healing. Previous studies have probed basal cell heterogeneity in stem/progenitor potential, but a non-biased dissection of basal cell dynamics during differentiation is lacking. Using single-cell RNA-sequencing coupled with RNAScope and fluorescence lifetime imaging, we identify three non-proliferative and one proliferative basal cell transcriptional states in homeostatic skin that differ in metabolic preference and become spatially partitioned during wound re-epithelialization. Pseudotemporal trajectory and RNA velocity analyses produce a quasi-linear differentiation hierarchy where basal cells progress from Col17a1 high /Trp63 high state to early response state, proliferate at the juncture of these two states, or become growth arrested before differentiating into spinous cells. Wound healing induces plasticity manifested by dynamic basalspinous interconversions at multiple basal states. Our study provides a systematic view of epidermal cellular dynamics supporting a revised "hierarchical-lineage" model of homeostasis.

Apoptosis recognition receptors regulate skin tissue repair in mice

“…In the skin, Timd4 is essential for allograft survival (Yeung et al 2013), which has been proposed to act through DCs to support Tregs. Indeed, Timd4 is expressed in DCs in later stages of wound repair (Haensel et al 2020). Our future studies will test the role of Timd4 on DCs and resident macrophages, T cell immunity, and how they impact wound repair phenotypes noted with Timd4 inhibition.…”

Phase-specific signatures of wound fibroblasts and matrix patterns define cancer-associated fibroblast subtypes

“…To investigate whether this early vs late wound fibroblast heterogeneity exists within and across wounds, we made use of available single cell RNA sequencing (scRNA)-seq datasets of murine wound fibroblasts (Table S1). We first re-analyzed cells from day-4 small mouse excisional wounds [25] (Fig. 2D) and calculated the early and late wound fibroblast signature scores across this dataset.…”