An integrated skin cell atlas decodes the pilosebaceous unit

Area of Science:

• Human tissue organization
• Single-cell and spatial transcriptomics
• Dermatology and regenerative medicine

Background:

• Human skin lacks a comprehensive, integrated cell atlas, especially for the pilosebaceous unit.
• Existing single-cell datasets are fragmented and lack standardized nomenclature.
• Understanding skin homeostasis and disease requires high-resolution mapping of its cellular components.

Purpose of the Study:

• To develop a scalable framework for a healthy Human Skin Cell Atlas (HSCA).
• To integrate diverse single-cell RNA sequencing datasets and spatial transcriptomics data.
• To create a comprehensive reference for healthy human skin cell types and their spatial organization.

Main Methods:

• Systematic integration of 34 public single-cell RNA sequencing datasets (819,068 cells).
• Harmonization of metadata and standardization of cell type nomenclature.
• Generation and integration of a high-resolution Visium HD spatial transcriptomics dataset.

Main Results:

• The HSCA revealed previously undetectable cell types, such as Merkel cells.
• Refined classification of pilosebaceous unit subtypes and identified critical signaling hubs.
• Demonstrated the value of integrating spatial and single-cell data for mapping tissue architecture.

Conclusions:

• The HSCA provides a comprehensive, expandable reference for healthy human skin.
• This integrated atlas facilitates rapid annotation of new datasets and discovery of rare cell types.
• The framework highlights the power of combined transcriptomic approaches for tissue studies and regenerative medicine.