Epigenetic Switch Reshapes Epithelial Stem/Progenitor Cells Signatures and Contributes to Inflammatory Programming in Hidradenitis Suppurativa [scRNA-seq]

In this study, we used single-cell RNA-sequencing to reveal how cellular heterogeneity of Hidradenitis Suppurativa (HS) lesional epidermis was reshaped at the transcriptional level. By comparison with healthy interfollicular epidermal basal cells, in HS we revealed marked gene signatures centered on mitotic chromosome segregation, DNA replication and repair as well as cell-cell adhesion and chromatic remodeling. Combing the pseudotime-ordered single-cell trajectory with the spatial localization analysis of defined basal cells, we further identified and validated a global alteration in cellular diversity within HS epidermis characterized by basal I-III cells hyperproliferation, concomitant decreases in superbasal keratinocytes, and phenotypic shifts toward the S100A cluster highly expressing pro-inflammatory genes S100A7/8/9. Cell-cell communication modeling suggested that HS BIII keratinocytes and S100A population serve as a crucial source to trigger IL-1 and IL-10 inflammatory cascades in the disease progression. Overall design: The Institutional Review Board of the University of Alabama at Birmingham approved the protocol (IRB-300005214) for obtaining surgically discarded skin tissues from heathy and HS (Hurley II/III stage) subjects. Surgical excisions from 7 patients with HS (axillary and groin lesions) and 5 healthy controls (discarded tissue from breast or abdominoplasty reduction surgery) were collected.