Integration of bulk and single-cell transcriptomics with spatial analysis identifies candidate hub genes and inferred regulatory programs in atopic dermatitis
- 1Department of Dermatology, The First Affiliated Hospital of Anhui Medical University , , ,
- 2Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University , , ,
Abstract
Background: Atopic dermatitis (AD) is a common chronic inflammatory disorder of the skin. Despite the availability of targeted biologics like dupilumab, heterogeneous treatment responses persist, highlighting the need for reliable biomarkers and a deeper understanding of cell-type-associated molecular programs within the tissue microenvironment.
Methods: This exploratory study integrated public microarray, single-cell RNA sequencing, and spatial transcriptomic datasets. GSE130588, comprising 124 lesional AD skin samples, was used for weighted gene co-expression network analysis (WGCNA). GSE59294 comprised 40 skin biopsies from 18 patients, including 16 pre-treatment lesional, 12 post-treatment lesional, 7 pre-treatment non-lesional, and 5 post-treatment non-lesional samples, and was used for differential expression analysis. The single-cell query cohort comprised 66,846 cells from 25 samples, with downstream analyses restricted to 19 blister-derived samples. Regulon activity was computationally inferred. GSE197023 comprised 20 spatial transcriptomic samples, including 7 lesional AD, 7 non-lesional AD, and 6 healthy-control samples, and was analyzed using cell-population deconvolution. CCR7 immunoreactivity was assessed by immunohistochemistry in independent healthy-control and lesional AD skin samples ( n = 5 per group) analyze.
Results: WGCNA identified disease-severity-associated gene modules enriched in immune and cell-cycle-related processes. Nominal- P -value-based integration with differential expression results identified seven exploratory candidate hub genes (GZMB, CCR7, GPR183, MMP12, IL7R, RGS1, and KLHDC7B) associated with immune- cell abundance patterns. FDR-adjusted sensitivity analysis supported MMP12 and RGS1 in the lesional-versus-non-lesional comparison, whereas none of the seven genes reached nominal or FDR-adjusted significance in the paired treatment analysis. Single-cell reference mapping showed cell-type-associated expression of GZMB in cytotoxic T-cell populations and CCR7 and MMP12 in dendritic-cell subsets. Computational regulon analysis identified candidate cell-type-associated regulatory signals and differences in inferred regulon activity across treatment-state groups. Spatial deconvolution indicated predominantly dermal distributions of inferred immune-cell populations. Immunohistochemical assessment showed higher relative CCR7 immunoreactivity in lesional AD skin than in healthy-control skin.
Conclusion: These cross-modal analyses linked candidate molecular signals todendritic-cell- and T- cell-associated patterns in AD. These findings are exploratory and hypothesis-generating and do not establish validated biomarkers, causal regulatory mechanisms, or predictors of treatment response. Independent cohort replication and functional and cell-type-specific validation are required.
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BibTeX
@article{chen2026integration,
title = {{Integration of bulk and single-cell transcriptomics with spatial analysis identifies candidate hub genes and inferred regulatory programs in atopic dermatitis}},
author = {Yuqiao Chen and Yulong Pan and Jiajie Chen and Li Lin and Shengxiu Liu},
journal = {Frontiers in immunology},
year = {2026},
month = sep,
doi = {10.3389/fimmu.2026.1863607},
url = {https://europepmc.org/article/PMC/PMC13661441},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integration of bulk and single-cell transcriptomics with spatial analysis identifies candidate hub genes and inferred regulatory programs in atopic dermatitis
AU - Yuqiao Chen
AU - Yulong Pan
AU - Jiajie Chen
AU - Li Lin
AU - Shengxiu Liu
PY - 2026
DA - 2026/09/30
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1863607
UR - https://europepmc.org/article/PMC/PMC13661441
AB - Background: Atopic dermatitis (AD) is a common chronic inflammatory disorder of the skin. Despite the availability of targeted biologics like dupilumab, heterogeneous treatment responses persist, highlighting the need for reliable biomarkers and a deeper understanding of cell-type-associated molecular programs within the tissue microenvironment. Methods: This exploratory study integrated public microarray, single-cell RNA sequencing, and spatial transcriptomic datasets. GSE130588, comprising 124 lesional AD skin samples, was used for weighted gene co-expression network analysis (WGCNA). GSE59294 comprised 40 skin biopsies from 18 patients, including 16 pre-treatment lesional, 12 post-treatment lesional, 7 pre-treatment non-lesional, and 5 post-treatment non-lesional samples, and was used for differential expression analysis. The single-cell query cohort comprised 66,846 cells from 25 samples, with downstream analyses restricted to 19 blister-derived samples. Regulon activity was computationally inferred. GSE197023 comprised 20 spatial transcriptomic samples, including 7 lesional AD, 7 non-lesional AD, and 6 healthy-control samples, and was analyzed using cell-population deconvolution. CCR7 immunoreactivity was assessed by immunohistochemistry in independent healthy-control and lesional AD skin samples ( n = 5 per group) analyze. Results: WGCNA identified disease-severity-associated gene modules enriched in immune and cell-cycle-related processes. Nominal- P -value-based integration with differential expression results identified seven exploratory candidate hub genes (GZMB, CCR7, GPR183, MMP12, IL7R, RGS1, and KLHDC7B) associated with immune- cell abundance patterns. FDR-adjusted sensitivity analysis supported MMP12 and RGS1 in the lesional-versus-non-lesional comparison, whereas none of the seven genes reached nominal or FDR-adjusted significance in the paired treatment analysis. Single-cell reference mapping showed cell-type-associated expression of GZMB in cytotoxic T-cell populations and CCR7 and MMP12 in dendritic-cell subsets. Computational regulon analysis identified candidate cell-type-associated regulatory signals and differences in inferred regulon activity across treatment-state groups. Spatial deconvolution indicated predominantly dermal distributions of inferred immune-cell populations. Immunohistochemical assessment showed higher relative CCR7 immunoreactivity in lesional AD skin than in healthy-control skin. Conclusion: These cross-modal analyses linked candidate molecular signals todendritic-cell- and T- cell-associated patterns in AD. These findings are exploratory and hypothesis-generating and do not establish validated biomarkers, causal regulatory mechanisms, or predictors of treatment response. Independent cohort replication and functional and cell-type-specific validation are required.
SN - 1664-3224
ER -