{
  "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.\n\nMethods: 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.\n\nResults: 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.\n\nConclusion: 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.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Dermatology, The First Affiliated Hospital of Anhui Medical University , , ,",
    "Department of Biochemistry and Molecular Biology, Metabolic Disease Research Center, School of Basic Medicine, Anhui Medical University , , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Yuqiao Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Yulong Pan"
    },
    {
      "affs": [
        0
      ],
      "name": "Jiajie Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Li Lin"
    },
    {
      "affs": [
        0
      ],
      "name": "Shengxiu Liu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/f27gwfxnag2e5.bib",
  "cited_by": 0,
  "doi": "10.3389/fimmu.2026.1863607",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661441/?tool=EBI",
  "id": "f27gwfxnag2e5",
  "issns": [
    "1664-3224"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13661441",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2708|Dermatology and Skin Diseases"
    ]
  ],
  "openalex": "W7214978420",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661441/pdf/?tool=EBI",
  "pmcid": "PMC13661441",
  "pmid": null,
  "published": "2026-09-30",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/f27gwfxnag2e5.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:21Z",
      "native_id": "PMC:PMC13661441",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13661441"
    },
    {
      "first_seen": "2026-10-30T12:19:15Z",
      "native_id": "10.3389/fimmu.2026.1863607",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1863607/full"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "issn:1664-3224",
      "subfield": "immunology"
    }
  ],
  "title": "Integration of bulk and single-cell transcriptomics with spatial analysis identifies candidate hub genes and inferred regulatory programs in atopic dermatitis",
  "title_text": "Integration of bulk and single-cell transcriptomics with spatial analysis identifies candidate hub genes and inferred regulatory programs in atopic dermatitis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:15Z",
  "url": "https://research.draconitic.com/paper/f27gwfxnag2e5",
  "venue": "Frontiers in immunology",
  "versions": []
}