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Mononuclear diploid cardiomyocytes support neonatal mouse heart regeneration in response to paracrine IGF2 signaling. Elife 2020 03 13;9

Date

03/14/2020

Pubmed ID

32167474

Pubmed Central ID

PMC7105374

DOI

10.7554/eLife.53071

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.

Author List

Shen H, Gan P, Wang K, Darehzereshki A, Wang K, Kumar SR, Lien CL, Patterson M, Tao G, Sucov HM

Author

Michaela Patterson PhD Assistant Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Animals, Newborn
Diploidy
Gene Expression Regulation
Genotype
Heart
Heart Injuries
Insulin-Like Growth Factor II
Mice
Mice, Knockout
Myocytes, Cardiac
Regeneration
Signal Transduction