Mononuclear diploid cardiomyocytes support neonatal mouse heart regeneration in response to paracrine IGF2 signaling
Mononuclear diploid cardiomyocytes support neonatal mouse heart regeneration in response to paracrine IGF2 signaling
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DOI：
10.7554/elife.53071
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发表时间：
2020-03
期刊：
影响因子：
7.7
通讯作者：
Hua Shen;Peiheng Gan;Peiheng Gan;Kristy Wang;A. Darehzereshki;Kai Wang;S. R. Kumar;C. Lien
中科院分区：
文献类型：
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作者：
Hua Shen;Peiheng Gan;Peiheng Gan;Kristy Wang;A. Darehzereshki;Kai Wang;S. R. Kumar;C. Lien
新生小鼠心脏的损伤可以有效地再生，但这种能力在出生后一周内就会丧失。我们发现IGF 2是心脏发育中重要的有丝分裂原，是新生儿心脏再生所必需的。IGF 2来源于内皮细胞/内皮细胞，并在心肌细胞中通过胰岛素受体转导。在出生后第1天损伤后，IGF 2的缺乏在出生后第一周的早期废除了损伤诱导的细胞周期进入。因此，再生失败，尽管后来存在额外的细胞周期诱导活动7天后损伤。大多数心肌细胞在出生后第一周从单核二倍体转变为多倍体。在三种不同的情况下，Igf 2缺陷的新生儿的再生得到了拯救，这些情况提高了出生后第7天单核二倍体心肌细胞的百分比。因此，IGF 2是一种旁分泌作用的有丝分裂原心脏再生在出生后早期，IGF 2缺乏揭示了这一进程的依赖增殖能力的单核二倍体心肌细胞。
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.