Mimicking Darier Disease In Vitro: A Human Epidermal Organoid Approach
Bibliographic record
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 migration and keratinocyte differentiation underscored the multifaceted disruption of epithelial integrity and homeostasis that defines DD pathology. Our work demonstrates that epidermal organoids derived from patients with Darier disease are a valuable model for studying DD. They provide a platform to study complex genetic epidermal disorders and personalised drug screening.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".