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

Lead Research Organisation: University of Cambridge
Department Name: Plant Sciences

Abstract

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.

Publications

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Studentship Projects

Project Reference Relationship Related To Start End Student Name
BB/M011194/1 01/10/2015 30/09/2023
1643619 Studentship BB/M011194/1 01/10/2015 30/09/2019 Lina Dobnikar
 
Description We discovered that regional transcriptional signatures of VSMCs from different parts of the aorta are present in each individual cell. In addition we discovered a rare subpopulation of VSMC, which express a progenitor marker Sca1. We defined a transcriptional signature of these cells and observed Sca1+ cells with equivalent signatures in the atherosclerotic plaque and after carotid ligation injury.
Exploitation Route Further studies of this cell population could identify ways in which VSMCs could be selectively stimulated or inhibited from proliferation in disease.
Sectors Healthcare

 
Description Biotechnology YES 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact As a team of 4 Babraham Institute PhD students we won the national competition Biotechnology YES in 2016.
Year(s) Of Engagement Activity 2016