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

Lina Dobnikar, Annabel L. Taylor, Joel Chappell, Phoebe Oldach, Jennifer L. Harman, Erin Oerton, Elaine Dzierzak, Martin R. Bennett, Mikhail Spivakov () and Helle F. Jørgensen ()
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Lina Dobnikar: Babraham Research Campus
Annabel L. Taylor: University of Cambridge, Cambridge Biomedical Campus
Joel Chappell: University of Cambridge, Cambridge Biomedical Campus
Phoebe Oldach: Babraham Research Campus
Jennifer L. Harman: University of Cambridge, Cambridge Biomedical Campus
Erin Oerton: Babraham Research Campus
Elaine Dzierzak: University of Edinburgh, Little France Crescent
Martin R. Bennett: University of Cambridge, Cambridge Biomedical Campus
Mikhail Spivakov: Babraham Research Campus
Helle F. Jørgensen: University of Cambridge, Cambridge Biomedical Campus

Nature Communications, 2018, vol. 9, issue 1, 1-17

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06891-x

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