A single-cell spatial transcriptomic census of human skin anatomy

ABSTRACT The skin is the largest human organ and a site of significant disease burden, yet its cellular and molecular organization across the body are largely undefined. Here, we construct a spatially-resolved single-cell atlas of 1.2 million cells from normal adult human skin to localize 45 cell types across 15 anatomic sites. We define principles of organ-wide cell composition, including axes of cell diversity and specialization, and distinguish site-enriched cell types. Each body site is comprised of 10 multicellular neighborhoods that define cell-cell communication. Notably, we identify a perivascular neighborhood enriched for immune-stromal crosstalk with features resembling a homeostatic immune niche similar to skin-associated lymphoid tissue. Finally, mapping these neighborhoods onto skin disease reveals pathogenic neighborhood disruptions, including pan-disease immune alterations in the perivascular neighborhood. We present a framework charting the skin’s multiscale spatial organization across a molecular to macroanatomic scale. This work advances our understanding of organ-wide skin cellular organization and communication, and its architectural disruption in disease. HIGHLIGHTS Human skin MERFISH spatial atlas of 1.2 million cells from 114 samples and 22 donors Cellular diversity varies along a central to peripheral body site spatial axis 10 multicellular neighborhoods define skin microanatomy and homeostatic interactions Human skin diseases feature spatial and transcriptional neighborhood remodeling Competing Interest Statement The authors have declared no competing interest. Footnotes ↵14 Lead Contact https://rstudio-connect.hpc.mssm.edu/humanskin-spatialcensus/