CDK9 Kinase Activation in Association with AFF1-SEC Initiates Epidermal Progenitor Differentiation

This study investigates the role of NCSTN gene mutations in Hidradenitis Suppurativa (HS) using skin organoids derived from induced pluripotent stem cells (iPSCs) of an HS patient. By correcting the mutation with CRISPR-Cas9, researchers created a control isogenic line. RNA-seq analysis revealed deregulated genes related to keratinocyte proliferation and differentiation in mutated organoids, along with higher expression of inflammatory cytokines and chemokines like IL1a, IL18, CCL20, and S100A7. These findings suggest that the NCSTN mutation leads to altered hair follicle stem cell differentiation and increased inflammatory protein expression, contributing to HS pathology.