After integrative analysis of scRNA-seq data from ascending aortic aneurysm tissue in Marfan syndrome mice and humans, Pedroza et al. characterized the disease-specific signature of modulated VSMCs, a distinct cluster of cell populations, which might be driven by TGF-β signaling and Klf4 overexpression (54). The gene discussed is KLF4; the disease is Marfan syndrome.