1. Developmental Biology
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Pericytes are progenitors for coronary artery smooth muscle

  1. Katharina S Volz
  2. Andrew H Jacobs
  3. Heidi I Chen
  4. Aruna Poduri
  5. Andrew S McKay
  6. Daniel P Riordan
  7. Natalie Kofler
  8. Jan Kitajewski
  9. Irving Weissman
  10. Kristy Red-Horse  Is a corresponding author
  1. Stanford University, United States
  2. Stanford Universitiy, United States
  3. Columbia University Medical Center, United States
Research Article
  • Cited 93
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Cite this article as: eLife 2015;4:e10036 doi: 10.7554/eLife.10036

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

  1. 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.
  2. Andrew H Jacobs

    Department of Biological Sciences, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Heidi I Chen

    Department of Biological Sciences, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Aruna Poduri

    Department of Biological Sciences, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrew S McKay

    Department of Biological Sciences, Stanford Universitiy, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Daniel P Riordan

    Department of Biochemistry, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Natalie Kofler

    Columbia University Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jan Kitajewski

    Columbia University Medical Center, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Irving Weissman

    Institute for Stem Cell and Regenerative Medicine, Ludwig Center, Stanford School of Medicine, Stanford University, Stanford, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. 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).

Reviewing Editor

  1. Giulio Cossu, University of Manchester, United Kingdom

Publication history

  1. Received: July 13, 2015
  2. Accepted: October 12, 2015
  3. Accepted Manuscript published: October 19, 2015 (version 1)
  4. 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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