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<p>The skin is the largest human organ and a site of substantial disease burden, yet its cellular and molecular organization across the body is largely undefined. Here we construct an organ-wide single-cell spatial atlas of ~1.2 million cells from normal adult human skin, resolving the location of 45 cell types across 114 samples encompassing 15 anatomic sites. We uncover site-specific stereotypic cell-type composition and their organization into ten multicellular neighborhoods, most notably a perivascular neighborhood reminiscent of skin-associated lymphoid tissue. Within this neighborhood, ligand–receptor (L–R) analyses identify a central role for tumor necrosis factor in maintaining <i>CCL19</i><sup>+</sup> perivascular fibroblasts, highlighting homeostatic immune–stromal crosstalk. Finally, comparing neighborhood dynamics in spatial transcriptomics of skin disease, we find pan-disease immune alterations in this perivascular neighborhood, suggesting spatial compartmentalization of pathogenic activity. Thus, multicellular neighborhoods underlie the skin’s multiscale molecular to macroanatomic organization, orchestrate cell–cell interactions and anatomic site specialization and exhibit architectural disruption in disease.</p>

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Single-cell spatial transcriptomic analysis of human skin anatomy

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年3月23日

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  • Paula Restrepo,
  • Alexis Wilder,
  • Aubrey Houser,
  • Harkirat Singh Sandhu,
  • Angie Ramirez,
  • M. Grace Hren,
  • Raman Gill,
  • Abiha Kazmi,
  • Larry Chen,
  • Alexandra Nigro,
  • Ichiro Imanishi,
  • Deniz Demircioglu,
  • Dan Hasson,
  • Alan Soto,
  • Stephanie McQuillan,
  • Edgar Gonzalez-Kozlova,
  • Rachel Brody,
  • Benjamin Ungar,
  • Maria Kasper,
  • Catherine P. Lu,
  • Philip Torina,
  • Jesse M. Lewin,
  • Sacha Gnjatic,
  • Sai Ma,
  • Andrew L. Ji

摘要

The skin is the largest human organ and a site of substantial disease burden, yet its cellular and molecular organization across the body is largely undefined. Here we construct an organ-wide single-cell spatial atlas of ~1.2 million cells from normal adult human skin, resolving the location of 45 cell types across 114 samples encompassing 15 anatomic sites. We uncover site-specific stereotypic cell-type composition and their organization into ten multicellular neighborhoods, most notably a perivascular neighborhood reminiscent of skin-associated lymphoid tissue. Within this neighborhood, ligand–receptor (L–R) analyses identify a central role for tumor necrosis factor in maintaining CCL19+ perivascular fibroblasts, highlighting homeostatic immune–stromal crosstalk. Finally, comparing neighborhood dynamics in spatial transcriptomics of skin disease, we find pan-disease immune alterations in this perivascular neighborhood, suggesting spatial compartmentalization of pathogenic activity. Thus, multicellular neighborhoods underlie the skin’s multiscale molecular to macroanatomic organization, orchestrate cell–cell interactions and anatomic site specialization and exhibit architectural disruption in disease.