436 Modelling darier disease using human epidermal organoids

Darier disease (DD) is a dominantly inherited skin disorder. It characterized by painful and malodourous plaques papules on the of patients. The typical features DD include: acantholysis abnormal keratinization. These histological are due to mutations in gene, ATP2A2, which encodes sarco/endoplasmic reticulum (ER) Ca2+-ATPase isoform 2 (SERCA2), pump ER. This leads malformation desmosomes adherent junctions. Currently, there no good vitro models study DD. An organoid collection organ-specific cells that develops from stem or progenitors capable recapitulating specific functions organ. Human epidermal organoids (HEOs) obtained epidermis have several advantages over 2D keratinocyte cultures. They an vivo-like complexity architecture ability recapitulate physiology epidermis. Exposure normal keratinocytes SERCA2 inhibitor thapsigargin (TG) recapitulated abnormalities observed HEOs exposed TG showed thus, In addition this artificial, chemical-induced model, we also developed HEO model derived isolated patients’ lesional biopsies as well generated with CRISPR-Cas9-modified primary keratinocytes. can be used screen for potential drugs treat pathomechanisms disease.