Pericytes are progenitors for coronary artery smooth muscle

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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.

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Katharina S Volz

Stem Cell and Regenerative Medicine PhD Program, Stanford University School of Medicine, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Andrew H Jacobs

Department of Biological Sciences, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Heidi I Chen

Department of Biological Sciences, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Aruna Poduri

Department of Biological Sciences, Stanford University, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Andrew S McKay

Department of Biological Sciences, Stanford Universitiy, Stanford, United States

Competing interests
The authors declare that no competing interests exist.
Daniel P Riordan

Department of Biochemistry, Stanford University, Stanford, United States

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The authors declare that no competing interests exist.
Natalie Kofler

Columbia University Medical Center, New York, United States

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The authors declare that no competing interests exist.
Jan Kitajewski

Columbia University Medical Center, New York, United States

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The authors declare that no competing interests exist.
Irving Weissman

Institute for Stem Cell and Regenerative Medicine, Ludwig Center, Stanford School of Medicine, Stanford University, Stanford, United States

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The authors declare that no competing interests exist.
Kristy Red-Horse

Department of Biological Sciences, Stanford University, Stanford, United States

For correspondence
kredhors@stanford.edu

Competing interests
The authors declare that no competing interests exist.

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).

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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.