Mononuclear diploid cardiomyocytes support neonatal mouse heart regeneration in response to paracrine IGF2 signaling
| Autor: | Ali Darehzereshki, Kristy Wang, Ching-Ling Lien, Henry M. Sucov, Michaela Patterson, Kai Wang, Peiheng Gan, Ge Tao, S. Ram Kumar, Hua Shen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
endocrine system diseases Mouse 030204 cardiovascular system & hematology Mice 0302 clinical medicine Myocytes Cardiac Biology (General) insulin receptor Mice Knockout biology Heart development General Neuroscience IGF2 Heart General Medicine Cell cycle female genital diseases and pregnancy complications medicine.anatomical_structure Medicine Research Article Signal Transduction animal structures heart regeneration Endothelium insulin-like growth factor 2 Genotype QH301-705.5 mononuclear diploid cardiomyocyte Science neonatal heart General Biochemistry Genetics and Molecular Biology Andrology 03 medical and health sciences Paracrine signalling Insulin-Like Growth Factor II medicine Animals Regeneration Endocardium General Immunology and Microbiology Regeneration (biology) Diploidy Insulin receptor 030104 developmental biology Animals Newborn Gene Expression Regulation Heart Injuries Insulin-like growth factor 2 biology.protein Developmental Biology |
| Zdroj: | eLife eLife, Vol 9 (2020) |
| ISSN: | 2050-084X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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