Compact Enhancer Logic Identified as Master Control of Fibroblast Activation in Fibrosis

Researchers have uncovered a compact regulatory architecture that governs fibroblast cell-state plasticity in fibrosis. Using CROP-seq to repress 280 conserved disease-activated enhancers across roughly 550,000 fibroblasts, they mapped 15 gene programs driving the profibrotic state, with the transcription factor MEOX1 emerging as a central regulator. In mice, fibroblast-specific deletion of Meox1 reduced fibrosis and improved cardiac function in heart failure. The study further showed that repressing just six of the enhancers with a multiplexed dCas12a-KRAB system was enough to collapse the profibrotic network and attenuate macrophage-driven inflammation. The findings, posted as a preprint on bioRxiv on October 17, 2026, suggest a route toward targeted epigenetic therapy for fibrotic disease. Peer review, replication, and translation to human fibrosis remain open questions.

Written by a model from the reports · updated 3 hours ago