Single-cell spatial transcriptomic analysis of human skin anatomy

Cite

Restrepo, P., Wilder, A., Houser, A., Sandhu, H. S., Ramirez, A., Grace Hren, M., Gill, R., Kazmi, A., Chen, L., Nigro, A., Imanishi, I., Demircioglu, D., Hasson, D., Soto, A., McQuillan, S., Gonzalez-Kozlova, E., Brody, R., Ungar, B., Kasper, M., … Ji, A. L. (2026). Single-cell spatial transcriptomic analysis of human skin anatomy. Nature Genetics.

https://doi.org/10.1038/s41588-026-02552-8

Abstract

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.

Datasets

1. Single-cell RNA-seq data

Explore
Sample ID
Sample source
Sample barcodes
Subject ID
Sex
Age
Skin region
Cell type (original)
Cell type (category)
Cell type (broad)
Cell type
Cell type (reclustered)
Age group
Disease
Assay
Reference genome
Harmonized clustering (res.2)
Harmonized clustering (res.2.5)
Harmonized clustering (res.4)
Harmonized clustering (res.1.2)
Harmonized clustering (res.8)
Harmonized clustering (res.6)
Harmonized clustering (res.2).1
Harmonized clustering (res.1.5)
Harmonized clustering (res.1)
Harmonized clustering (res.5
Seurat clustering
Tissue
Ganier_PNAS_202470,231 cells
JC45,210 cells
ZZ43,952 cells
AJ21,186 cells
Brunner2316,441 cells
Brunner2014,494 cells
SoleBoldo_CommunBiol_202013,634 cells
Weidemann_CellReports_202311,985 cells
TT7,309 cells
YuImmunity2024_NS-axillar5,943 cells
RT4,752 cells
VorstandlechnerNatComms2021_NS-023,502 cells
YuImmunity2024_NS-groin2,970 cells
TST012,399 cells
NST011,427 cells
A1046M1,139 cells
A1038LM971 cells
VorstandlechnerNatComms2021_NS-01925 cells
A1022M557 cells
CST01551 cells
A1011L542 cells
VorstandlechnerNatComms2021_NS-03435 cells
A1020LM301 cells
A1021M295 cells
A1025L281 cells
A1016LM281 cells
A1033M267 cells
A1026L261 cells
A1014L245 cells
A1012M167 cells
EZ03149 cells
A1015LM143 cells
A1017LM94 cells
CST0366 cells
NST0363 cells
TST0310 cells
Single-cell spatial transcriptomic analysis of human skin anatomy

2. Visium ST data

Explore
Sample source
Subject ID
Sample ID
Disease group
Disease
Skin region
Age
Sex
Skin region detailed
Assay
Ethnicity
Tissue
Age group
Seurat clustering
Harmonized clustering (res.2)
Harmonized clustering (res.2.5)
Harmonized clustering (res.8)
Harmonized clustering (res.2).1
Harmonized clustering (res.4)
Harmonized clustering (res.5)
Harmonized clustering (res.1.5)
Harmonized clustering (res.6)
Harmonized clustering (res.1.2)
Harmonized clustering (res.1)
GanierPNAS202445,673 cells
YuImmunity202441,219 cells
ThraneJID202315,016 cells
MitamuraAllergy202313,740 cells
BergenstrahleNatBiotech202210,374 cells
JiCell20208,924 cells
MaNatComms20247,569 cells
Single-cell spatial transcriptomic analysis of human skin anatomy

3. MERFISH data

Explore
Sample label
Segmentation method
Run region
Batch ID
Gene panel
Run name
Region name
Subject ID
Sex
Skin region
Sample collection source
SCVI batch
Run name (short)
Cell type (predicted ID)
Cell type (broad)
Cell type (category)
Cell type
Tissue neighborhood
Age
Ethnicity
RIN
Sample preservation method
Sample collection method
Sample compartment
Tissue annotation
Sample ID
Age group
Assay
Disease
cellcharter clustering (k_11)
cellcharter clustering (k_15)
cellcharter clustering (k_19)
cellcharter clustering (k_35)
cellcharter clustering (k_34)
scvi leiden clustering (0.8)
cellcharter clustering (k_12)
cellcharter clustering (k_25)
cellcharter clustering (k_26)
scvi leiden clustering (2.5)
cellcharter clustering (k_30)
scvi leiden clustering (2)
cellcharter clustering (k_23)
cellcharter clustering (k_3)
cellcharter clustering (k_33)
cellcharter clustering (k_13)
scvi leiden clustering (1)
scvi leiden clustering (0.5)
cellcharter clustering (k_21)
cellcharter clustering (k_14)
cellcharter clustering (k_22)
scvi leiden clustering (0.4)
cellcharter clustering (k_32)
cellcharter clustering (k_18)
cellcharter clustering (k_31)
cellcharter clustering (k_5)
scvi leiden clustering (1.5)
scvi leiden clustering (0.6)
cellcharter clustering (k_27)
cellcharter clustering (k_16)
cellcharter clustering (k_2)
cellcharter clustering (k_6)
cellcharter clustering (k_10)
cellcharter clustering (k_8)
cellcharter clustering (k_9)
cellcharter clustering (k_24)
cellcharter clustering (k_7)
cellcharter clustering (k_4)
cellcharter clustering (k_28)
cellcharter clustering (k_29)
cellcharter clustering (k_20)
scvi leiden clustering (0.2)
cellcharter clustering (k_17
Tissue
202304121534_MSSM-Ji-Skin3-VA227_VMSC02701_region_0103,786 cells
202304141439_MSSM-Ji-Skin2-VA227_VMSC02701_region_071,958 cells
202308311115_D041-43--lastprobes-083123_VMSC02301_region_159,743 cells
202306121431_AH21-NS-ConcClear-061223_VMSC02301_region_048,053 cells
202306070957_AH21-NSFFPE-060723-AH_VMSC02301_region_034,056 cells
202404041030_D165--1-6--04042024_VMSC02301_region_233,650 cells
202312131041_D077--1-4--12132023_VMSC02301_region_324,738 cells
202402221100_D151-1-6--fullrun--rerun--02222024_VMSC02301_region_324,405 cells
202404041030_D165--1-6--04042024_VMSC02301_region_424,183 cells
202402221100_D151-1-6--fullrun--rerun--02222024_VMSC02301_region_423,992 cells
202404151153_Panniculectomy--D048-D142---04152024_VMSC02301_region_122,169 cells
202404041030_D165--1-6--04042024_VMSC02301_region_320,582 cells
202407031037_D134-D173--OTR-NS--07032024_VMSC02301_region_016,460 cells
202404241001_D165--7-12--04242024_VMSC02301_region_515,230 cells
202403281041_D145--1-6--03282024_VMSC02301_region_414,731 cells
202312131041_D077--1-4--12132023_VMSC02301_region_214,572 cells
202404241001_D165--7-12--04242024_VMSC02301_region_414,413 cells
202404241001_D165--7-12--04242024_VMSC02301_region_113,824 cells
202405141034_D149--1-6--rerun--05142024_VMSC02301_region_313,638 cells
202404041030_D165--1-6--04042024_VMSC02301_region_012,846 cells
202403180949_D107--7-12--03182024_VMSC02301_region_012,491 cells
202310301133_D082--1-4--10302023_VMSC02301_region_312,166 cells
202402221100_D151-1-6--fullrun--rerun--02222024_VMSC02301_region_512,043 cells
202404241001_D165--7-12--04242024_VMSC02301_region_011,895 cells
202309281027_AutopsyBFFPE092823_VMSC02301_region_111,293 cells
202404111130_D145--7-12--04112024_VMSC02301_region_011,077 cells
202403121435_D107--1-6--03122024_VMSC02301_region_410,781 cells
202310301133_D082--1-4--10302023_VMSC02301_region_210,700 cells
202404241001_D165--7-12--04242024_VMSC02301_region_210,513 cells
202312131041_D077--1-4--12132023_VMSC02301_region_110,476 cells
202404241001_D165--7-12--04242024_VMSC02301_region_310,341 cells
202407031037_D134-D173--OTR-NS--07032024_VMSC02301_region_510,280 cells
202404151153_Panniculectomy--D048-D142---04152024_VMSC02301_region_29,800 cells
202404151153_Panniculectomy--D048-D142---04152024_VMSC02301_region_48,833 cells
202405111530_D077--6-12--05112024_VMSC02301_region_08,711 cells
202403180949_D107--7-12--03182024_VMSC02301_region_48,453 cells
202309281027_AutopsyBFFPE092823_VMSC02301_region_28,370 cells
202402221100_D151-1-6--fullrun--rerun--02222024_VMSC02301_region_18,078 cells
202403121435_D107--1-6--03122024_VMSC02301_region_38,064 cells
202312180956_D077--5-8--12182023_VMSC02301_region_17,641 cells
202403211122_D083--1-6-032124_VMSC02301_region_37,636 cells
202404151153_Panniculectomy--D048-D142---04152024_VMSC02301_region_07,568 cells
202310301133_D082--1-4--10302023_VMSC02301_region_17,538 cells
202404301517_D149--7-12--04302024_VMSC02301_region_07,495 cells
202404111130_D145--7-12--04112024_VMSC02301_region_47,447 cells
202404111130_D145--7-12--04112024_VMSC02301_region_37,348 cells
202403121435_D107--1-6--03122024_VMSC02301_region_57,335 cells
202404301517_D149--7-12--04302024_VMSC02301_region_27,321 cells
202404301517_D149--7-12--04302024_VMSC02301_region_57,270 cells
202404151153_Panniculectomy--D048-D142---04152024_VMSC02301_region_37,240 cells
202309281027_AutopsyBFFPE092823_VMSC02301_region_07,047 cells
202403151059_D151--7-12--03152024_VMSC02301_region_37,029 cells
202402221100_D151-1-6--fullrun--rerun--02222024_VMSC02301_region_07,026 cells
202309281027_AutopsyBFFPE092823_VMSC02301_region_36,986 cells
202311011251_D082--5-8--11012023_VMSC02301_region_36,879 cells
202404111130_D145--7-12--04112024_VMSC02301_region_56,811 cells
202403211122_D083--1-6-032124_VMSC02301_region_56,730 cells
202405111530_D077--6-12--05112024_VMSC02301_region_36,726 cells
202403151059_D151--7-12--03152024_VMSC02301_region_16,709 cells
202403281041_D145--1-6--03282024_VMSC02301_region_36,659 cells
202404301517_D149--7-12--04302024_VMSC02301_region_36,321 cells
202405111530_D077--6-12--05112024_VMSC02301_region_46,315 cells
202311011251_D082--5-8--11012023_VMSC02301_region_26,301 cells
202404041030_D165--1-6--04042024_VMSC02301_region_56,284 cells
202405111530_D077--6-12--05112024_VMSC02301_region_16,262 cells
202405081011_D082--4-12--05082024_VMSC02301_region_46,157 cells
202403211122_D083--1-6-032124_VMSC02301_region_46,143 cells
202404301517_D149--7-12--04302024_VMSC02301_region_46,127 cells
202405141034_D149--1-6--rerun--05142024_VMSC02301_region_46,047 cells
202403180949_D107--7-12--03182024_VMSC02301_region_35,954 cells
202403281041_D145--1-6--03282024_VMSC02301_region_05,954 cells
202403151059_D151--7-12--03152024_VMSC02301_region_05,950 cells
202403281041_D145--1-6--03282024_VMSC02301_region_55,870 cells
202405081011_D082--4-12--05082024_VMSC02301_region_25,812 cells
202402221100_D151-1-6--fullrun--rerun--02222024_VMSC02301_region_25,716 cells
202405081011_D082--4-12--05082024_VMSC02301_region_35,632 cells
202403151059_D151--7-12--03152024_VMSC02301_region_45,429 cells
202310301133_D082--1-4--10302023_VMSC02301_region_05,414 cells
202312131041_D077--1-4--12132023_VMSC02301_region_05,378 cells
202312180956_D077--5-8--12182023_VMSC02301_region_05,365 cells
202405141034_D149--1-6--rerun--05142024_VMSC02301_region_15,333 cells
202404111130_D145--7-12--04112024_VMSC02301_region_25,323 cells
202405081011_D082--4-12--05082024_VMSC02301_region_55,316 cells
202403121435_D107--1-6--03122024_VMSC02301_region_05,127 cells
202404301517_D149--7-12--04302024_VMSC02301_region_15,126 cells
202404151153_Panniculectomy--D048-D142---04152024_VMSC02301_region_55,079 cells
202311011251_D082--5-8--11012023_VMSC02301_region_15,012 cells
202404041030_D165--1-6--04042024_VMSC02301_region_14,930 cells
202407031037_D134-D173--OTR-NS--07032024_VMSC02301_region_14,922 cells
202405111530_D077--6-12--05112024_VMSC02301_region_54,897 cells
202405111530_D077--6-12--05112024_VMSC02301_region_24,875 cells
202403281041_D145--1-6--03282024_VMSC02301_region_24,822 cells
202405141034_D149--1-6--rerun--05142024_VMSC02301_region_04,803 cells
202405111530_D077--6-12--05112024_VMSC02301_region_64,698 cells
202405141034_D149--1-6--rerun--05142024_VMSC02301_region_24,619 cells
202405081011_D082--4-12--05082024_VMSC02301_region_04,588 cells
202403180949_D107--7-12--03182024_VMSC02301_region_54,349 cells
202407031037_D134-D173--OTR-NS--07032024_VMSC02301_region_34,286 cells
202403180949_D107--7-12--03182024_VMSC02301_region_14,119 cells
202403151059_D151--7-12--03152024_VMSC02301_region_23,881 cells
202403211122_D083--1-6-032124_VMSC02301_region_03,550 cells
202403121435_D107--1-6--03122024_VMSC02301_region_23,518 cells
202403121435_D107--1-6--03122024_VMSC02301_region_13,323 cells
202404111130_D145--7-12--04112024_VMSC02301_region_13,293 cells
202403151059_D151--7-12--03152024_VMSC02301_region_53,086 cells
202405081011_D082--4-12--05082024_VMSC02301_region_12,842 cells
202403180949_D107--7-12--03182024_VMSC02301_region_22,811 cells
202405141034_D149--1-6--rerun--05142024_VMSC02301_region_52,529 cells
202312180956_D077--5-8--12182023_VMSC02301_region_22,431 cells
202403281041_D145--1-6--03282024_VMSC02301_region_12,070 cells
202311011251_D082--5-8--11012023_VMSC02301_region_01,856 cells
202312180956_D077--5-8--12182023_VMSC02301_region_31,851 cells
202403211122_D083--1-6-032124_VMSC02301_region_21,291 cells
202403211122_D083--1-6-032124_VMSC02301_region_11,064 cells
Single-cell spatial transcriptomic analysis of human skin anatomy

Alias names

S-BIAD2376