Genomic, transcriptomic and proteomic depiction of iPSC-derived smooth muscle cells as emerging cellular models for arterial diseases

Vascular smooth muscle cells (SMCs) plasticity is a central mechanism in cardiovascular health and disease. We aimed at providing deep cellular phenotyping, epigenomic and proteomic depiction of SMCs derived from induced pluripotent stem cells (iPSCs) and evaluating their potential as cellular models in the context of complex genetic arterial diseases.We differentiated 3 human iPSCs lines using either RepSox (R-SMCs) or PDGF-BB and TGF-beta (TP-SMCs), during the second half of a 24-days-long protocol. Both iPSC differentiation protocols generated SMCs with positive expression of SMC markers. TP-SMCs exhibited greater capacity of proliferation, migration and lower calcium release in response to contractile stimuli compared to R-SMCs. We performed RNA-Seq and assay for transposase accessible chromatin (ATAC)-Seq at 6 time-points of differentiation. RNA-Seq data showed that genes involved in the contractile function of arteries were highly expressed in R-SMCs compared to TP-SMCs or primary SMCs.These two iPSC-derived SMCs models present complementary cellular phenotypes of high relevance to SMC plasticity. Our data supports the use of these cellular models to study complex regulatory mechanisms at genetic risk loci involved in several arterial diseases.