Single-Nucleus Chromatin Accessibility Identifies a Critical Role for TWIST1 in IPF Myofibroblast Activity

Multiomic single-cell analyses on human IPF lungs identify a global opening of TWIST1 and other E-box motifs in IPF myofibroblasts, with in vivo murine models confirming a critical regulatory function for TWIST1 in IPF myofibroblast activity. Overall design: We performed single-nucleus ATAC sequencing (snATAC-seq) on explanted lungs from patients with IPF (n=3) and donor controls (n=2) and integrated this with a larger scRNA-seq dataset (n=10 IPF, 8 control) to identify differentially accessible chromatin regions and enriched TF motifs within lung cell populations. We performed RNA-sequencing on pulmonary fibroblasts of bleomycin-injured Twist1-overexpressing Col1a2 Cre-ER mice to examine alterations in fibrosis-relevant pathways following Twist1 overexpression in collagen producing cells. This Series includes human samples.