Precardiac deletion of Numb and Numblike reveals renewal of cardiac progenitors

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Cite this article as: eLife 2014;3:e02164 doi: 10.7554/eLife.02164

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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

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Lincoln T Shenje

Johns Hopkins University, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Peter Andersen

Johns Hopkins University, Baltimore, United States

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The authors declare that no competing interests exist.
Hideki Uosaki

Johns Hopkins University, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Laviel Fernandez

Johns Hopkins University, Baltimore, United States

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The authors declare that no competing interests exist.
Peter P Rainer

Johns Hopkins University, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Gun-sik Cho

Johns Hopkins University, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Dong-ik Lee

Johns Hopkins University, Baltimore, United States

Competing interests
The authors declare that no competing interests exist.
Weimin Zhong

Yale University, New Haven, United States

Competing interests
The authors declare that no competing interests exist.
Richard P Harvey

Victor Chang Cardiac Research Institute, Darlinghurst, Australia

Competing interests
The authors declare that no competing interests exist.
David A Kass

Johns Hopkins University, Baltimore, United States

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The authors declare that no competing interests exist.
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

Robb Krumlauf, Stowers Institute for Medical Research, United States

Publication history

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

Copyright

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.