{"database":"GEO","file_versions":[],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE328048"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Single-cell transcriptome reveals keratinocyte subclusters that contribute to altered differentiation and inflammatory responses in atopic dermatitis","description":"Atopic dermatitis (AD) is a common chronic inflammatory skin disease with complex, poorly understood pathogenesis due to its mechanistic heterogeneity. 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. 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.","dates":{"publication":"2026/06/01"},"accession":"GSE328048","cross_references":{"GSM":["GSM9671104","GSM9671103","GSM9671069","GSM9671102","GSM9671101","GSM9671068","GSM9671067","GSM9671100","GSM9671066","GSM9671065","GSM9671064","GSM9671063","GSM9671062","GSM9671061","GSM9671060","GSM9671079","GSM9671078","GSM9671077","GSM9671076","GSM9671075","GSM9671074","GSM9671073","GSM9671072","GSM9671071","GSM9671070","GSM9670989","GSM9670996","GSM9670995","GSM9671049","GSM9670994","GSM9670993","GSM9671048","GSM9670992","GSM9671047","GSM9671046","GSM9670991","GSM9670990","GSM9671045","GSM9671044","GSM9671043","GSM9671042","GSM9671041","GSM9671040","GSM9670999","GSM9670998","GSM9670997","GSM9671059","GSM9671058","GSM9671057","GSM9671056","GSM9671055","GSM9671054","GSM9671053","GSM9671052","GSM9671051","GSM9671050","GSM9671019","GSM9671029","GSM9671028","GSM9671027","GSM9671026","GSM9671025","GSM9671024","GSM9671023","GSM9671022","GSM9671021","GSM9671020","GSM9671039","GSM9671038","GSM9671037","GSM9671036","GSM9671035","GSM9671034","GSM9671033","GSM9671032","GSM9671031","GSM9671030","GSM9671007","GSM9671006","GSM9671005","GSM9671004","GSM9671003","GSM9671002","GSM9671089","GSM9671001","GSM9671088","GSM9671000","GSM9671087","GSM9671086","GSM9671085","GSM9671084","GSM9671083","GSM9671082","GSM9671081","GSM9671080","GSM9671090","GSM9671009","GSM9671008","GSM9671018","GSM9671017","GSM9671016","GSM9671015","GSM9671014","GSM9671013","GSM9671012","GSM9671099","GSM9671011","GSM9671098","GSM9671010","GSM9671097","GSM9671096","GSM9671095","GSM9671094","GSM9671093","GSM9671092","GSM9671091"],"GPL":["24676"],"GSE":["328048"],"taxon":["Homo sapiens"]}}