MYRF Controls Mesothelium Specification, Signaling, and Plasticity [CUT&Run]

The mesothelium is a squamous monolayer that ensheathes internal organs and lines the body cavities. Aside from facilitating tissue sliding, its additional functions remain poorly understood. Here, we study the mesothelium through investigating myelin regulatory factor (Myrf), a transcription factor expressed in the mesothelium and a top mutated gene in congenital diaphragmatic hernia (CDH), a developmental disorder that affects the lung and diaphragm. In mice, inactivation of Myrf early in embryogenesis resulted in CDH and defective mesothelium specification, compromising its role as a signaling center for lung growth. Inactivation after mesothelium specification led to additional defects, including enhanced differentiation into various mesenchymal cell types, causing a striking accumulation of elastin-expressing smooth muscle/myofibroblasts encasing the lung, mimicking pleuroparenchymal fibroelastosis (PPFE), a rare adult lung condition. Compound mutants demonstrate that MYRF functions synergistically with YAP/TAZ in mesothelium differentiation. Together, these findings highlight the complex role of the mesothelium in development and disease. Overall design: E16.5 wildtype mesothelial cells were stained with surface markers and sorted by flow cytometry for H3K27ac CUT&RUN.