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


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Authors
Dobnikar, Lina 
Chappell, Joel 
Oldach, Phoebe 
Harman, Jennifer L 
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.

Description
Keywords
Animals, Aorta, Ataxin-1, Carotid Arteries, Cell Lineage, Disease Susceptibility, Gene Expression Profiling, Mice, Muscle, Smooth, Vascular, Myocytes, Smooth Muscle, Plaque, Atherosclerotic, Sequence Analysis, RNA, Single-Cell Analysis, Transcriptome
Journal Title
Nat Commun
Conference Name
Journal ISSN
2041-1723
2041-1723
Volume Title
9
Publisher
Springer Science and Business Media LLC
Sponsorship
British Heart Foundation (CH/2000003)
British Heart Foundation (CH/2000003/12800)
British Heart Foundation (via University of Oxford) (AVRYMZO)
Biotechnology and Biological Sciences Research Council (1643619)
British Heart Foundation (None)
British Heart Foundation (None)
BBSRC (1501561)
Wellcome Trust (100574/Z/12/Z)
British Heart Foundation (FS/15/38/31516)
British Heart Foundation (None)
British Heart Foundation (None)
British Heart Foundation (PG/16/11/32021)
British Heart Foundation (PG/16/63/32307)
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0405)
Biotechnology and Biological Sciences Research Council (BBS/E/B/000C0404)
BHF