biorxiv.org· Zhu, A. M., Li, Y., Zhang, H., Rathinasabapathi, B., Cimarosti, B., Nadadur, R., Xu, V., Huang, Y., An, Y., Auclair, K., Mahr, A., Sheth, M. U., Lee, C. Y., Wang, C., Yamawaki, T., Pelonero, A., Padmanabhan, A., Ranade, S. S., Engreitz, J. M., Ason, B., Li, C.-M., Jackson, S., Amrute, J. M., Przytycki, P. F., Alexanian, M. ·2026-10-16 08:00· 1 day agoPickScore63

A Compact Regulatory Logic Governs Fibroblast Cell State Plasticity in Fibrosis

In brief

A compact regulatory logic controls fibroblast activation in fibrosis: repressing 280 conserved disease-activated enhancers via CROP-seq in ~550,000 fibroblasts mapped 15 gene programs governing the profibrotic state, converging on MEOX1 as a central regulator. Fibroblast-specific Meox1 deletion in mice improved cardiac function and reduced fibrosis in heart failure. Repressing just six enhancers with multiplexed dCas12a-KRAB collapsed the profibrotic network and attenuated macrophage inflammation.

Why it matters

It reduces fibroblast activation to a small set of enhancers and one transcription factor, enabling targeted reprogramming of fibrosis.

Source: biorxiv.org · biorxiv.org

#Preprint #Epigenetics #Chromatin & 3D genome #Cardiometabolic