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Nat Commun. 2018 Nov 1;9(1):4567. doi: 10.1038/s41467-018-06891-x.

Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels.

Author information

1
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK.
2
Division of Cardiovascular Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK.
3
Sir William Dunn School of Pathology, University of Oxford, South Parks Rd, Oxford, OX1 3RE, UK.
4
Centre for Molecular Informatics, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK.
5
MRC Centre for Inflammation Research, University of Edinburgh, Little France Crescent, Edinburgh, EH16 4TJ, UK.
6
Nuclear Dynamics Programme, Babraham Institute, Babraham Research Campus, Cambridge, CB22 3AT, UK. mikhail.spivakov@lms.mrc.ac.uk.
7
Functional Gene Control Group, Epigenetics Section, MRC London Institute of Medical Sciences, Du Cane Road, London, W12 0NN, UK. mikhail.spivakov@lms.mrc.ac.uk.
8
Institute of Clinical Sciences, Faculty of Medicine, Imperial College, Du Cane Road, London, W12 0NN, UK. mikhail.spivakov@lms.mrc.ac.uk.
9
Division of Cardiovascular Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, CB2 0QQ, UK. hfj22@cam.ac.uk.

Abstract

Vascular smooth muscle cells (VSMCs) show pronounced heterogeneity across and within vascular beds, with direct implications for their function in injury response and atherosclerosis. Here we combine single-cell transcriptomics with lineage tracing to examine VSMC heterogeneity in healthy mouse vessels. The transcriptional profiles of single VSMCs consistently reflect their region-specific developmental history and show heterogeneous expression of vascular disease-associated genes involved in inflammation, adhesion and migration. We detect a rare population of VSMC-lineage cells that express the multipotent progenitor marker Sca1, progressively downregulate contractile VSMC genes and upregulate genes associated with VSMC response to inflammation and growth factors. We find that Sca1 upregulation is a hallmark of VSMCs undergoing phenotypic switching in vitro and in vivo, and reveal an equivalent population of Sca1-positive VSMC-lineage cells in atherosclerotic plaques. Together, our analyses identify disease-relevant transcriptional signatures in VSMC-lineage cells in healthy blood vessels, with implications for disease susceptibility, diagnosis and prevention.

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