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Related Experiment Video

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Cell Population Analyses During Skin Carcinogenesis
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Single-cell spatial transcriptomic analysis of human skin anatomy.

Paula Restrepo1,2,3, Alexis Wilder2,3, Aubrey Houser1,2,3

  • 1Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.

Nature Genetics
|March 24, 2026
PubMed
Summary

This study maps human skin cells, revealing ten distinct multicellular neighborhoods and their organization. These neighborhoods are crucial for skin function and show disrupted immune activity in disease.

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Area of Science:

  • Dermatology
  • Cell Biology
  • Immunology

Background:

  • The skin's cellular and molecular organization is largely undefined despite its role as the largest human organ.
  • Understanding skin structure is crucial for addressing its substantial disease burden.

Purpose of the Study:

  • To create a comprehensive single-cell spatial atlas of normal adult human skin.
  • To define cell types, their locations, and their organization into multicellular neighborhoods across different anatomic sites.
  • To investigate immune-stromal interactions and identify disease-associated alterations in skin architecture.

Main Methods:

  • Single-cell RNA sequencing and spatial transcriptomics were used.
  • Analysis of approximately 1.2 million cells from 114 human skin samples across 15 anatomic sites.
  • Ligand-receptor interaction analysis to identify cell-cell communication pathways.

Main Results:

  • A spatial atlas of 45 distinct cell types was constructed.
  • Ten stereotypic multicellular neighborhoods were identified, including a perivascular neighborhood resembling skin-associated lymphoid tissue.
  • Tumor necrosis factor was identified as key in maintaining perivascular fibroblasts, indicating immune-stromal crosstalk.
  • Spatial transcriptomics revealed pan-disease immune alterations within the perivascular neighborhood in skin diseases.

Conclusions:

  • Multicellular neighborhoods are fundamental to skin organization, cell interactions, and site specialization.
  • These neighborhoods exhibit disrupted architecture in disease states.
  • The perivascular neighborhood is a key site for immune-stromal interactions and disease pathogenesis.