Atherosclerosis is the leading cause of death in the Western world and better understanding of the disease promoting mechanisms are needed. Especially, we are far from understanding the role of vascular smooth muscle cells (VSMCs) and fibroblasts (FBs) in the disease progression. Recent evidence suggests that VSMCs and FBs display extraordinary plasticity and can acquire foam cell or myofibroblast-like features that are associated with plaque instability.
In this study we aim to bring the characterization of the phenotypic spectrum of VSMCs and FBs to date by analyzing alterations in cell subtypes using single cell RNA-sequencing. CRISPR-based screening of the phenotype transitions is further used to identify transcription factors and signaling pathways that could explain the pathological transformation of cells. Ultimately, this study will provide markers of disease-associated cell states while identifying targets for future therapies.