Omics · study · 2026
Single-cell transcriptome reveals keratinocyte subclusters that contribute to altered differentiation and inflammatory responses in atopic dermatitis
Listed in NCBI GEO
Atopic dermatitis (AD) is a common chronic inflammatory skin disease with complex, poorly understood pathogenesis due to its mechanistic heterogeneity.
Description
To investigate underlying mechanisms, we performed single-cell RNA sequencing (scRNA-seq) on lesional (LAD) and non-lesional (NAD) skin from 42 AD patients and skin from 23 healthy controls (HC). Keratinocytes (KCs) were the most abundant cell type identified.
In healthy skin, KC differentiation followed a linear trajectory from basal KCs (BKs) through seven differentiated stages (DK1–DK7) to terminal keratinized cells (KK1 and KK2). In LAD, this process was disrupted, showing a reversed transition from KK2 to KK1, mainly driven by DK7. APOD and LYZ were identified as LAD-specific regulators of this aberrant keratinization, linked to IL-13- and IL-22-driven responses involving endoplasmic reticulum (ER) stress and oxidative damage.
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Mitochondrial and ER dysfunction were specifically enriched in LAD DK6 cells, suggesting this subcluster as a key pathogenic compartment associated with cytokine activation. Further, cell-cell interaction analysis (validated through Xenium spatial transcriptomics and immunohistochemistry) highlighted TWEAK, derived from IL13+ Th2 and cycling T cells acting on FN14+ basal and differentiated KCs, as a key contributor to AD-associated epidermal responses.
These findings reveal how disrupted KC differentiation and specific immune pathways contribute to AD pathogenesis, identifying distinct cellular compartments and inflammatory circuits as potential therapeutic targets.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE328nnn/GSE328048 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328048 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1453562 ncbi.nlm.nih.gov/bioproject/PRJNA1453562 ↗
project · from NCBI GEO
- PubMed 42449103 pubmed.ncbi.nlm.nih.gov/42449103 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Expression profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
- Inferred from text
- Disease 75% · RNA sequencing 75% · Sequencing 75% · Single-cell RNA sequencing 75%
Provenance · 1 source records, 11 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE328048 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[disease].local:disease:disease | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:expression-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[modality].local:modality:rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:sequencing | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[modality].local:modality:single-cell-rna-seq | enrichment · NCBI GEO | keyword-concept-rules@1.0.0 | title+description (75%) |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |