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Comprehensive single-cell transcriptomic profiling of the scalp from patients with moderate-to-severe alopecia areata

GSE316832 Homo sapiens Expression profiling by high throughput sequencing 30 samples Submitted 2026/03/16 Platform GPL34281
Summary
Background: Alopecia areata (AA) is an autoimmune hair loss disorder characterized by follicular destruction. While bulk transcriptomic studies have identified contributory inflammatory axes, specific cell pathways remain underexplored. Objective: To characterize the single-cell transcriptomic landscape underpinning AA scalp compared to healthy controls. Methods: We performed single-cell RNA-sequencing on lesional and nonlesional scalp biopsies from 13 patients with moderate-to-severe AA (5 with alopecia totalis/universalis [AT/AU]) and 11 healthy controls. Results: Overall, we profiled 41,067 high-quality cells. Lesional AA samples demonstrated robust Th1 activation and cytotoxicity, with upregulated IFNG, GZMH/K, and XCL1/2. Concurrently, Th2 skewing (IL13, IL13RA1, IL4R) and TNFRSF4/OX40 elevations in lesional CD4+ and regulatory T-cells were also observed. IL15, JAK2/3, and STAT1 levels were increased in distinct lesional dendritic cell subsets, with JAK/STAT genes also upregulated in fibroblasts and keratinocytes. Fibroblasts and smooth muscle cells exhibited enriched pro-inflammatory and pro-fibrotic markers (CXCL9, CCL26, POSTN, COL5A3, COL6A6). Lesional keratinocytes further demonstrated downregulated hair keratins and increased interferon signaling. AA endothelial cells showed increased angiogenic and interferon signatures. Compared to patchy AA and controls, AT/AU demonstrated higher expression of multiple cytotoxic, Th1, Th2, and JAK/STAT markers in immune cells, and proliferative and inflammatory signatures in non-immune cells. Conclusion: This comprehensive high-resolution single-cell map uncovers potential communication networks between immune and non-immune cell populations in AA scalp, possibly disrupting immune privilege at the hair follicle and driving disease progression and/or severity. Clinical Implications: These data provide single-cell-resolution insights into AA pathogenesis and potential molecular targets for precision therapies tailored to AA severity.
Published in
Comprehensive single-cell transcriptomic profiling of the scalp from patients with moderate-to-severe alopecia areata
Hu BD, He H, Bose S et al. · The Journal of allergy and clinical immunology 2026 · PMID 41740930 · doi:10.1016/j.jaci.2026.02.014
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Direct links to NCBI, no account and no request form: the whole study as GSE316832_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 30 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA1404311 and SRA study SRP663899. Searching any of these in the dataset finder brings you back here.

Study design
30 conditions, each sampled once — no replicated groups

Supports a case/control comparison: 19 samples read as cases, 11 as controls.

Read from 30 sample titles: 30 distinct titles with little repetition. Check it against the sample list below before relying on it.

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