Skin Cell Heterogeneity in Development, Wound Healing, and Cancer

Abstract

Skin architecture and function depend on diverse populations of epidermal cells and dermal fibroblasts. Reciprocal communication between the epidermis and dermis plays a key role in skin development, homeostasis and repair. While several stem cell populations have been identified in the epidermis with distinct locations and functions, it is now recognised that there is additional heterogeneity within the mesenchymal cells of the dermis. Here, we discuss recent insights into how these distinct cell populations are maintained and coordinated during development, homeostasis, and wound healing. We highlight the importance of the local environment, or niche, in cellular plasticity. We also discuss new mechanisms that have been identified as influencing wound repair and cancer progression.

Multi‐tasking epidermal stem cells: Beyond epidermal maintenance

“…It is now clear that dermal fibroblasts are more heterogeneous than previously thought (Driskell & Watt, ; Rognoni & Watt, ). One of the most well‐characterized fibroblast populations associated with the epidermis is the dermal papilla, which are essential for hair follicle morphogenesis and regeneration.…”

“…It is now clear that dermal fibroblasts are more heterogeneous than previously thought (Driskell & Watt, 2015;Rognoni & Watt, 2018).…”

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

“…The different criteria used for stem/progenitor fate assignment (often linked to the specific techniques used), such as molecular differentiation markers, basal layer residence status, and assumptions about stem-cell-division or clonal-growth kinetics, may account for the differences in data interpretation (Gonzales and Fuchs, 2017). Moreover, the observed epidermal stem cell heterogeneity in mouse back skin may reflect different cellular states of a single differentiation program (Rognoni and Watt, 2018). Clearly, genome-wide transcriptomic and in situ analyses with single-cell resolution are needed to provide a comprehensive, non-biased picture of basal cell heterogeneity, to unravel previously unknown cellular states and their transitions during epidermal lineage differentiation, and to seek unifying principles of epidermal homeostasis.…”

“…Wound healing represents a highly regulated process composed of several distinct but overlapping stages (inflammation, re-epithelialization, and resolution) that involve the coordinated activities of epidermal, dermal, immune and endothelial cells (Gurtner et al, 2008). Re-epithelialization is driven by spatially patterned migration and proliferation of epidermal cells at the wound periphery, as well as migration and dedifferentiation/reprogramming of hair follicle (HF) and sebaceous gland epithelial cells (Haensel and Dai, 2018;Park et al, 2017;Rognoni and Watt, 2018).…”

“…What and how epidermal cells migrate during wound re-epithelialization were a subject of debate, with two different models being proposed in the past: 1) basal cells first migrate into the wound bed and unidirectionally convert into suprabasal cells; and 2) wound peripheral epidermal cells crawl or "leapfrog" over one another such that suprabasal cells migrate in and become basal cells (Rittié, 2016;Rognoni and Watt, 2018). Recent live cell imaging and lineage tracing studies have provided clarity to this issue by defining distinct zones of epidermal cellular activities in the wound area: a migratory zone next to the wound margin where both basal and suprabasal cells move towards the wound center, an intermediate, mixed zone of coordinated migration and proliferation, and a hyperproliferative zone furthest away from the wound margin (Aragona et al, 2017;Park et al, 2017).…”