A genome-wide, single-cell analysis of vascular smooth muscle cell plasticity

Vascular smooth muscle cells (VSMCs) are major components of blood vessel walls, where they regulate blood flow and blood pressure. In response to inflammation and injury in the blood vessels, VSMCs can change into a so-called 'synthetic' state, whereby they become migratory, proliferate and take part in tissue repair. This unusual plasticity of VSMCs is vital for the maintenance of healthy vasculature throughout the lifespan. Individual VSMCs appear to differ in their capacity to switch to a synthetic phenotype and show heterogeneity in the levels of contractile VSMC markers. Intriguingly, these cells also originate from two different embryonic tissues, and origin-specific differences in their 'eagerness' to undergo phenotypic switching in response to injury have been observed. We therefore hypothesise that individual VSMCs are differentially 'primed' for this response depending on both their embryonic origin and yet unknown factors, and that their differential plasticity is reflected by their global gene expression profiles. The project aims to further elucidate the mechanisms underlying VSMC plasticity. It will first take advantage of the state-of-the-art method of single-cell RNA sequencing (scRNAseq) to profile gene expression genome-wide in multitudes of individual VSMCs. A comprehensive bioinformatics interrogation of the scRNAseq data will then be carried out to formulate hypotheses on the potential genes and gene networks that underlie VSMC plasticity. Finally, these hypotheses will be tested experimentally in vitro and in vivo. Bioinformatics data analysis is integral to the project, but the balance between the experimental and computational work can be adjusted to suit the candidate's objectives.