AI Article Synopsis
- - The study investigates the plasticity of vascular smooth muscle cells (SMCs) using induced pluripotent stem cells (iPSCs) differentiated into two types (R-SMCs and TP-SMCs) through different protocols, providing insights into their potential for cardiovascular research.
- - Both SMC types showed key smooth muscle markers, with TP-SMCs demonstrating better proliferation and migration, while R-SMCs had stronger contractile functionality linked to arterial health.
- - The findings reveal that these iPSC-derived SMC models are crucial for understanding the genetic factors contributing to major arterial diseases, with specific gene expressions and protein profiles distinguishing their roles.
Article Abstract
Background: Vascular smooth muscle cells (SMCs) plasticity is a central mechanism in cardiovascular health and disease. We aimed at providing cellular phenotyping, epigenomic and proteomic depiction of SMCs derived from induced pluripotent stem cells and evaluating their potential as cellular models in the context of complex diseases.
Methods: Human induced pluripotent stem cell lines were differentiated using RepSox (R-SMCs) or PDGF-BB (platelet-derived growth factor-BB) and TGF-β (transforming growth factor beta; TP-SMCs), during a 24-day long protocol. RNA-Seq and assay for transposase accessible chromatin-Seq were performed at 6 time points of differentiation, and mass spectrometry was used to quantify proteins.
Results: Both induced pluripotent stem cell differentiation protocols generated SMCs with positive expression of SMC markers. TP-SMCs exhibited greater proliferation capacity, migration and lower calcium release in response to contractile stimuli, compared with R-SMCs. Genes involved in the contractile function of arteries were highly expressed in R-SMCs compared with TP-SMCs or primary SMCs. R-SMCs and coronary artery transcriptomic profiles were highly similar, characterized by high expression of genes involved in blood pressure regulation and coronary artery disease. We identified and as key drivers of RepSox specific program. Extracellular matrix content contained more proteins involved in wound repair in TP-SMCs and higher secretion of basal membrane constituents in R-SMCs. Open chromatin regions of R-SMCs and TP-SMCs were significantly enriched for variants associated with blood pressure and coronary artery disease.
Conclusions: Both induced pluripotent stem cell-derived SMCs models present complementary cellular phenotypes of high relevance to SMC plasticity. These cellular models present high potential to study functional regulation at genetic risk loci of main arterial diseases.
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| http://dx.doi.org/10.1161/HYPERTENSIONAHA.122.19733 | DOI Listing |
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