Defining Epidermal Basal Cell States During Skin Homeostasis and Wound Healing Using Single-Cell Transcriptomics

Abstract

Highlights d scRNA-seq identifies four epidermal basal cell states in homeostatic adult skin d Computational analysis supports a ''hierarchical'' model of epidermal homeostasis d Basal cell states are metabolically distinct and spatially partitioned in wounded skin d Epidermal basal cells show enhanced cell fate and state plasticity during wound healing

The hallmarks of cancer are also the hallmarks of wound healing

“…Gene expression studies in the regenerating Xenopus laevis tadpole show that many genes linked to glycolytic metabolism are locally induced here also (116). Single-cell transcriptomic analysis of mouse skin wounds indicates major alterations in the expression of metabolism-associated genes, with a reduction in transcripts associated with oxidative phosphorylation and a complementary increase in transcripts associated with glycolysis in subpopulations of cells at the wound edge (117). Studies in the regenerating zebrafish heart also show evidence for cardiomyocytes in the border zone at the edge of a wound reprogramming their metabolism, suggesting that metabolic plasticity might explain why fish cardiac tissues can repair so much more efficiently than their mammalian equivalents, because blockade of this metabolic switch impairs fish heart repair (118).…”

Murine interfollicular epidermal differentiation is gradualistic with GRHL3 controlling progression from stem to transition cell states

“…Gene lists in Supplementary Data 1. h Gene ontology categories of genes differentially expressed at E16. 5 suggesting that GRHL3 plays an important role in promoting the differentiation of IFE.B to IFE.T cells. These findings suggest: (1) Normal IFE differentiation proceeds in a smooth, continuous manner rather than in punctuated stages.…”

“…Meanwhile, mesoderm-derived immune cells and neural crest-derived melanocytes take up residence in the epidermis. Although IFE heterogeneity and differentiation have been previously studied with single cell RNAsequencing (scRNA-seq) in adult mouse and human skin [1][2][3][4][5] , late development of the embryonic IFE has not been studied with scRNA-seq, and key gene regulators of IFE differentiation have not been systematically identified with this method.…”

Epidermal Stem Cells in Hair Follicle Cycling and Skin Regeneration: A View From the Perspective of Inflammation

“…According to the first, the cells of the basal layer migrate to the wound bed and then differentiate into suprabasal, and according to the second, suprabasal cells move from wound edges to the wound bed due to “leapfrog” mechanism and become basal ( Rognoni and Watt, 2018 ). Thereby, epidermal cells possess certain plasticity: they can undergo de-differentiation as well as differentiation under the influence of accompanying wound healing inflammatory agents ( Haensel et al, 2020 ). Noteworthy, similar transitions are known in inflammatory diseases.…”

“…This indicated increased plasticity of cell fate in the skin sample of wounded mice with bidirectional transitions in several cell states between basal and spinous cells, which was not observed in the non-wounded animals. Thus, the wound inflammatory milieu stimulates epidermal cell plasticity and enfeebles restrictions on cell differentiation compared to their non-wounded counterparts ( Haensel et al, 2020 ).…”