Pericytes are progenitors for coronary artery smooth muscle
- Stanford University, United States
- Stanford Universitiy, United States
- Columbia University Medical Center, United States
Abstract
Epicardial cells on the heart's surface give rise to coronary artery smooth muscle cells (caSMCs) located deep in the myocardium. However, the differentiation steps between epicardial cells and caSMCs are unknown as are the final maturation signals at coronary arteries. Here, we use clonal analysis and lineage tracing to show that caSMCs derive from pericytes, mural cells associated with microvessels, and that these cells are present in adults. During development following the onset of blood flow, pericytes at arterial remodeling sites upregulate Notch3 while endothelial cells express Jagged-1. Deletion of Notch3 disrupts caSMC differentiation. Our data support a model wherein epicardial-derived pericytes populate the entire coronary microvasculature, but differentiate into caSMCs at arterial remodeling zones in response to Notch signaling. Our data is the first demonstration that pericytes are progenitors for smooth muscle, and their presence in adult hearts reveal a new potential cell type for targeting during cardiovascular disease.
Article and author information
Author details
Reviewing Editor
- Giulio Cossu, University of Manchester, United Kingdom
Ethics
Animal experimentation: All animal experiments were performed according to protocols approved by the Stanford University Institutional Animal Care and Use Committee (IACUC) under the protocol #26923 (Assurance #A3213-01). The laboratory animal care program at Stanford University is fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC).
Version history
- Received: July 13, 2015
- Accepted: October 12, 2015
- Accepted Manuscript published: October 19, 2015 (version 1)
- Version of Record published: December 23, 2015 (version 2)
Copyright
© 2015, Volz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Pericytes are progenitors for coronary artery smooth muscle
eLife 4:e10036.
https://doi.org/10.7554/eLife.10036
Further reading
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- Chromosomes and Gene Expression
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Developmental programming involves the accurate conversion of signalling levels and dynamics to transcriptional outputs. The transcriptional relay in the Notch pathway relies on nuclear complexes containing the co-activator Mastermind (Mam). By tracking these complexes in real time, we reveal that they promote the formation of a dynamic transcription hub in Notch ON nuclei which concentrates key factors including the Mediator CDK module. The composition of the hub is labile and persists after Notch withdrawal conferring a memory that enables rapid reformation. Surprisingly, only a third of Notch ON hubs progress to a state with nascent transcription, which correlates with polymerase II and core Mediator recruitment. This probability is increased by a second signal. The discovery that target-gene transcription is probabilistic has far-reaching implications because it implies that stochastic differences in Notch pathway output can arise downstream of receptor activation.
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