Mimicking Darier Disease In Vitro: A Human Epidermal Organoid Approach.

ABSTRACT: Darier disease (DD) is a rare genetic disorder caused by mutations in the ATP2A2 gene, resulting in calcium dysregulation and impaired keratinocyte adhesion. Due to the paucity of suitable models, understanding the molecular mechanisms of DD has been challenging. In this study, we developed a human epidermal organoid model derived from DD patient keratinocytes to investigate the molecular and phenotypic features of the disease. The model recapitulates key aspects of DD pathology, including acantholysis, desmosomal dysfunction and barrier disruption, with mislocalisation of desmosomal proteins. Furthermore, the transcriptomic landscape of DD organoids reflected broad perturbations in epidermal structure. Enrichment of pathways associated with epidermal development, cell adhesion, cell migra

SUBMITTER: Agarwal R 

PROVIDER: S-EPMC12749551 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature