The authors followed the Cheung protocol to generate embryonic lineage-specific SMC which enabled them to recapitulate the pathology seen in Marfan aortas, including defects in fibrillin-1 (FBN1) accumulation, ECM degradation, TGFβ signaling, contraction and apoptosis finally resulting in aortic aneurysms in Marfan syndrome patients. Here, FBN1 is linked to Marfan syndrome.