Disease-relevant transcriptional signatures identified in individual smooth muscle cells from healthy mouse vessels
Year: 2018
Type: article
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.
Source: Nature Communications
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,827
Funders: Wellcome Trust, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research, National Institute for Health and Care Research, British Heart Foundation, Medical Research Council, Biotechnology and Biological Sciences Research Council, European Research Council
Awards: Assessment and effects of cell senescence in vascular disease, G2018687014, Computational systems biology of ageing in haematopoiesis and the immune system, G2176452781, Genomic and epigenomic analysis of ageing in haematopoiesis and the immune system., G2813349254, Institute of Metabolic Science., Cambridge 2nd intake 2014 – 4-year PhD Studentship (3rd) Scheme: Ms Jessica Beeson; Mr Ross Lindsay; Mr Cai Read; Ms Jessica Rees, Cambridge 3rd intake 2015 – 4-year PhD Studentship (3rd) Scheme: Ms Sarah Burgess; Ms Sophie McManus; Mr Joshua Hodgson; Ms Annabel Taylor, Institute of Metabolic Science., G4798798426, Epigenetic regulation of smooth muscle cell genes, G5093058308, G5219940826, G5408067991, BHF Centre of Regenerative Medicine funded by our Mending Broken Hearts Appeal, A genome-wide, single-cell analysis of vascular smooth muscle cell plasticity, Regulation of vascular smooth muscle cell apoptosis and cell senescence in atherosclerosis, Functional analysis of H3K9-methylation on gene regulation and phenotypic switching in vascular smooth muscle cells, G7850449913, Research Excellence, G834046340
OpenAlex ID: W2898549090