Troy/Tnfrsf19 marks epidermal cells that govern interfollicular epidermal renewal and cornification.

Kai Kretzschmar,Susana M Chuva De Sousa Lopes,Priyanca Asra,Margit Bleijs,Kim E Boonekamp,Hans Clevers,Barbara Giovannone,Mandy Koomen

doi:10.1016/j.stemcr.2021.07.007

Abstract

SummaryThe skin epidermis is a highly compartmentalized tissue consisting of a cornifying epithelium called the interfollicular epidermis (IFE) and associated hair follicles (HFs). Several stem cell populations have been described that mark specific compartments in the skin but none of them is specific to the IFE. Here, we identify Troy as a marker of IFE and HF infundibulum basal layer cells in developing and adult human and mouse epidermis. Genetic lineage-tracing experiments demonstrate that Troy-expressing basal cells contribute to long-term renewal of all layers of the cornifying epithelium. Single-cell transcriptomics and organoid assays of Troy-expressing cells, as well as their progeny, confirmed stem cell identity as well as the ability to generate differentiating daughter cells. In conclusion, we define Troy as a marker of epidermal basal cells that govern interfollicular epidermal renewal and cornification.

Highlights

Mammalian skin acts as a protective mechanical and biological barrier against injuries, foreign pathogens, and loss of heat and water
TROY marks interfollicular and infundibular epidermal cells in telogen skin Based on consensus data generated by the Human Protein Atlas program (Uhlen et al, 2015), we found that the skin was the human tissue with the second highest normalized expression of TROY (Figure 1A)
At embryonic day 12.5 (E12.5), when the epidermis is an undifferentiated layer between the periderm and dermis, enhanced green fluorescent protein (EGFP) expression in back skin was confined to epidermal cells (Figure 1F)

Summary

Introduction

Mammalian skin acts as a protective mechanical and biological barrier against injuries, foreign pathogens, and loss of heat and water. Critical to the skin’s main function is its outermost layer, the epidermis, which is comprised of a multi-layered epithelium, the interfollicular epidermis (IFE), and associated hair follicles (HFs), sebaceous glands (SGs), and sweat glands (in mice only in the paws). Exposed to the body’s outside is the cornified envelope of the epidermis, known as the stratum corneum. This epidermal layer consists of enucleated, organelle-free cells, which are enriched in highly crosslinked filamentous keratins and other cytoskeletal proteins in their cytoplasm. The stratified squamous epithelium of the IFE is heavily studied using cultured human and murine keratinocytes or mouse models to explore adult homeostasis and perturbations, such as wounding or diseases

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