1. Developmental Biology and Stem Cells
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Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors

  1. Lincoln T Shenje
  2. Peter Andersen
  3. Hideki Uosaki
  4. Laviel Fernandez
  5. Peter P Rainer
  6. Gun-sik Cho
  7. Dong-ik Lee
  8. Weimin Zhong
  9. Richard P Harvey
  10. David A Kass
  11. Chulan Kwon Is a corresponding author
  1. Johns Hopkins University, United States
  2. Yale University, United States
  3. Victor Chang Cardiac Research Institute, Australia
Research Article
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Cite as: eLife 2014;3:e02164 doi: 10.7554/eLife.02164

Abstract

Cardiac progenitor cells (CPCs) must control their number and fate to sustain the rapid heart growth during development, yet the intrinsic factors and environment governing these processes remain unclear. Here, we show that deletion of the ancient cell-fate regulator Numb (Nb) and its homologue Numblike (Nbl) depletes CPCs in second pharyngeal arches (PA2s) and is associated with an atrophic heart. With histological, flow cytometric and functional analyses, we find that CPCs remain undifferentiated and expansive in the PA2, but differentiate into cardiac cells as they exit the arch. Tracing of Nb- and Nbl-deficient CPCs by lineage-specific mosaicism reveals that the CPCs normally populate in the PA2, but lose their expansion potential in the PA2. These findings demonstrate that Nb and Nbl are intrinsic factors crucial for the renewal of CPCs in the PA2 and that the PA2 serves as a microenvironment for their expansion

Article and author information

Author details

  1. Lincoln T Shenje

    Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Peter Andersen

    Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Hideki Uosaki

    Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Laviel Fernandez

    Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Peter P Rainer

    Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Gun-sik Cho

    Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Dong-ik Lee

    Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Weimin Zhong

    Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Richard P Harvey

    Victor Chang Cardiac Research Institute, Darlinghurst, Australia
    Competing interests
    The authors declare that no competing interests exist.
  10. David A Kass

    Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Chulan Kwon

    Johns Hopkins University, Baltimore, United States
    For correspondence
    ckwon13@jhmi.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All the animals were treated humanely according to AALAC and NIH guidelines (Johns Hopkins Medical Institutions are fully accredited by the AALAC) and the current study was conducted under the animal protocol (MO10M444) approved by the Animal Care and Use Committee at Johns Hopkins University.

Reviewing Editor

  1. Robb Krumlauf, Reviewing Editor, Stowers Institute for Medical Research, United States

Publication history

  1. Received: December 27, 2013
  2. Accepted: April 1, 2014
  3. Accepted Manuscript published: April 24, 2014 (version 1)
  4. Version of Record published: May 6, 2014 (version 2)

Copyright

© 2014, Shenje et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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