Mononuclear diploid cardiomyocytes support neonatal mouse heart regeneration in response to paracrine IGF2 signaling
- University of Southern California, United States
- Medical University of South Carolina, United States
- Children's Hospital Los Angeles, United States
- First Affiliated Hospital of Guangzhou Medical University, China
- Medical College of Wisconsin, United States
Abstract
Injury to the newborn mouse heart is efficiently regenerated, but this capacity is lost by one week after birth. We found that IGF2, an important mitogen in heart development, is required for neonatal heart regeneration. IGF2 originates from the endocardium/endothelium and is transduced in cardiomyocytes by the insulin receptor. Following injury on postnatal day 1, absence of IGF2 abolished injury-induced cell cycle entry during the early part of the first postnatal week. Consequently, regeneration failed despite the later presence of additional cell cycle-inducing activities 7 days following injury. Most cardiomyocytes transition from mononuclear diploid to polyploid during the first postnatal week. Regeneration was rescued in Igf2-deficient neonates in three different contexts that elevate the percentage of mononuclear diploid cardiomyocytes beyond postnatal day 7. Thus, IGF2 is a paracrine-acting mitogen for heart regeneration during the early postnatal period, and IGF2-deficiency unmasks the dependence of this process on proliferation-competent mononuclear diploid cardiomyocytes.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Michaela Patterson
Funding
National Institutes of Health (HL070123)
- Henry Sucov
American Heart Association (17SDG33400141)
- Ge Tao
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocol 10173 of the University of Southern California and protocols 2018-00642 and 2018-00310 of the Medical University of South Carolina.
Reviewing Editor
- Caroline E Burns, Boston Children's Hospital, United States
Version history
- Received: October 28, 2019
- Accepted: March 12, 2020
- Accepted Manuscript published: March 13, 2020 (version 1)
- Version of Record published: March 30, 2020 (version 2)
Copyright
© 2020, Shen 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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Mononuclear diploid cardiomyocytes support neonatal mouse heart regeneration in response to paracrine IGF2 signaling
eLife 9:e53071.
https://doi.org/10.7554/eLife.53071
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