545 Skin Organoids derived from NCSTN mutated patient-induced pluripotent stem cells recapitulate Hidradenitis Suppurativa pathogenic hallmarks

Hidradenitis Suppurativa (HS) is an inflammatory skin disease started by hair follicle epithelial stem cells that proliferate in uncontrolled manner, forming a keratin plug the and interconnected tendrils dermis. These processes are accompanied infiltration of neutrophils Th17 HS lesions. Mutations NCSTN gene have been associated with HS, but lack vitro models for pilosebaceous unit hinders study its role pathogenesis. We thus developed organoids from induced pluripotent (iPSCs) obtained patient nonsense mutation NCSTN. corrected using CRISPR-Cas9 technique to obtain iPSC isogenic line as control. RNA-seq analysis comparing mutated non-mutated showed enrichment deregulated genes implicated keratinocyte proliferation differentiation. also observed significant higher expression some cytokine chemokine organoids, including IL1a, IL18, CCL20 S100A7, which responsible activation skin. 3D-imaging follicles less organised structure confirming differentiation defect. An increased number layers thicker epithelium were reconstructed organoid-isolated cells, impairment keratinocytes. In conclusion, IPSCs-derived HS-associated results alteration cell proteins hallmarks.