Single-Cell and Spatial Transcriptomic Analysis of Human Skin Delineates Intercellular Communication and Pathogenic...

Area of Science:

• Dermatology and Molecular Biology
• Investigating the molecular mechanisms of skin homeostasis and disease.
• Utilizing single-cell and spatial transcriptomics for high-resolution skin tissue analysis.

Background:

• Epidermal homeostasis relies on keratinocyte balance, but cross-species mechanisms and disease links are unclear.
• Understanding species-specific differences in skin biology is crucial for deciphering disease pathogenesis.
• Existing knowledge gaps hinder the development of targeted therapies for skin disorders.

Purpose of the Study:

• To elucidate conserved and divergent mechanisms of epidermal homeostasis across species.
• To identify novel cell subpopulations and pathways contributing to skin diseases.
• To create a valuable resource for skin research.

Main Methods:

• Integrated human and mouse skin single-cell RNA sequencing and spatial transcriptomics data.
• Improved human skin cell-type annotation using spatial transcriptomics.
• Performed cross-species comparative analyses and cell-of-origin enrichment analysis.

Main Results:

• Identified a human-specific spinous keratinocyte subpopulation with proliferative capacity and heavy metal processing functions.
• This subpopulation was expanded in psoriasis and zinc-deficiency dermatitis, suggesting disease relevance.
• Nominated pathogenic cell subpopulations and communication pathways in genodermatoses, revealing potential therapeutic targets.

Conclusions:

• A novel human skin cell subpopulation plays a role in epidermal homeostasis and disease.
• Dysfunction of specific cell subpopulations may be a hallmark of skin diseases.
• The integrated dataset and web resource will advance mechanistic and translational skin research.