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Perturb-seq resolves physiologic programs and bidirectional regulation of non-canonical NF-κB signaling in epidermal organoids

Squiers, G.; Nanes, B. A.; Balas, M.; Lingo, J. J.; Wang, L.; Zhou, H.; Munawar, S.; Nzima, M.; Hon, G. C.; Klein, J.

2026-07-23 genomics
10.64898/2026.07.22.739901 bioRxiv
Show abstract

Regulated keratinocyte differentiation is required for formation of the stratified epidermis and a functional barrier. Understanding genetic drivers of keratinocyte differentiation is crucial for understanding several skin diseases. Perturb-seq is a single-cell CRISPR screen that measures transcriptomic responses to perturbations. To date, Perturb-seq experiments have principally focused on 2-dimensional cell culture models lacking hallmarks of skin development - physiological desmosome formation and barrier function. Here, we leverage Perturb-seq in an epidermal organoid model that recapitulates physiologically relevant differentiation programs. We demonstrate that our perturbations significantly impact diverse differentiation programs and reveal bidirectional function of non-canonical NF-{kappa}B signaling in late keratinocyte differentiation.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.