GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE314nnn/GSE314972/primaryOK200TranscriptomicsHomo sapiensExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE314972GEOGSEfalseSingle-cell transcriptomic profiling of frontal fibrosing alopecia reveals preserved cellular architecture with stress-driven epithelial reprogramming and non-cytotoxic inflammationBackground: Frontal fibrosing alopecia (FFA) is a primary cicatricial alopecia characterised by progressive follicular fibrosis and irreversible hair loss. Despite increasing clinical recognition, the cellular mechanisms sustaining disease persistence remain incompletely defined. Objectives: To define cell-type–specific transcriptional states and inter-compartmental signalling networks in lesional scalp from patients with FFA using single-cell RNA sequencing. Methods: Single-cell RNA sequencing was performed on lesional scalp biopsies from patients with FFA (n = 4) and matched control samples (n = 4). Cells were annotated into major lineages and refined subpopulations, and functional programmes and ligand–receptor-mediated communication were analysed. Results: Analysis of 38,984 high-quality cells revealed preservation of overall cellular composition and lineage architecture in FFA compared with controls. Despite this stability, marked disease-associated transcriptional reprogramming was observed across epithelial, immune and stromal compartments. Keratinocytes retained compartment-specific identity but exhibited prominent activation of stress-response and inflammatory pathways, particularly within upper follicle and bulge/outer root sheath populations. Dermal fibroblasts aligned along a continuous inflammation–fibrosis axis, with relative expansion of inflammatory and ACTA2⁺ states and strengthened coupling between inflammatory and fibrotic programmes. Immune profiling demonstrated skewing of CD4⁺ T cells towards Th1-, Th2- and Th22-associated signatures, together with macrophage reprogramming towards pro-fibrotic, tissue-remodelling states. Ligand–receptor analysis identified TGFB-centred signalling as the dominant inter-compartmental communication axis linking epithelial stress to immune modulation and fibroblast activation. Conclusions: FFA exhibits preserved cellular architecture but extensive, compartment-specific transcriptional reprogramming. Chronic epithelial stress and TGFB-driven inter-compartmental signalling, rather than overt cytotoxic inflammation, emerge as central disease mechanisms.2026/06/29GSE314972GSM9419469GSM9419468GSM9419474GSM9419473GSM9419475GSM9419470GSM9419472GSM941947124676314972Homo sapiens