Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish.
Myocardial Polyploidization Creates a Barrier to Heart Regeneration in Zebrafish.
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DOI：
10.1016/j.devcel.2018.01.021
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发表时间：
2018-02-26
影响因子：
11.8
通讯作者：
Burns CG
中科院分区：
文献类型：
--
作者：
González-Rosa JM;Sharpe M;Field D;Soonpaa MH;Field LJ;Burns CE;Burns CG
相关证据表明，在出生后哺乳动物中自然发生的心肌多倍化对心脏再生造成了障碍。在这里，我们超越了相关性，证明斑马鱼心肌细胞的实验多倍化足以抑制其在再生过程中的增殖潜力。最初，我们确定，斑马鱼心肌变得容易多倍体化后，瞬时胞质分裂抑制介导的显性负Ect 2。使用转基因策略，我们产生了成年动物含有马赛克心脏组成的差异标记的二倍体和多倍体富集的心肌细胞群体。二倍体心肌细胞在产生再生心肌方面胜过其多倍体邻居。此外，由同等比例的二倍体和多倍体心肌细胞组成的心脏无法完全再生，这表明需要临界百分比的二倍体心肌细胞才能实现心脏再生。我们的数据确定心肌细胞多倍化是心脏再生的障碍，并表明动员人类心脏中罕见的二倍体心肌细胞将提高其再生能力。目前还不清楚为什么某些非哺乳动物物种能有效地再生心脏，而哺乳动物却不能。Gonzalez-Rosa等人证明，简单地增加高度再生的斑马鱼心肌的DNA含量，使其更接近哺乳动物的DNA含量，就足以抑制心肌细胞的增殖能力和器官再生。
Correlative evidence suggests that polyploidization of heart muscle, which occurs naturally in post-natal mammals, creates a barrier to heart regeneration. Here, we move beyond a correlation by demonstrating that experimental polyploidization of zebrafish cardiomyocytes is sufficient to suppress their proliferative potential during regeneration. Initially, we determined that zebrafish myocardium becomes susceptible to polyploidization upon transient cytokinesis inhibition mediated by dominant negative Ect2. Using a transgenic strategy, we generated adult animals containing mosaic hearts composed of differentially labeled diploid and polyploid-enriched cardiomyocyte populations. Diploid cardiomyocytes outcompeted their polyploid neighbors in producing regenerated heart muscle. Moreover, hearts composed of equivalent proportions of diploid and polyploid cardiomyocytes failed to regenerate altogether, demonstrating that a critical percentage of diploid cardiomyocytes is required to achieve heart regeneration. Our data identify cardiomyocyte polyploidization as a barrier to heart regeneration and suggest that mobilizing rare diploid cardiomyocytes in the human heart will improve its regenerative capacity. It remains unclear why certain non-mammalian species efficiently regenerate their hearts, while mammals fail in this endeavor. Gonzalez-Rosa et al. demonstrate that simply increasing the DNA content of the highly regenerative zebrafish myocardium, to more closely resemble that in mammals, is sufficient to dampen cardiomyocyte proliferative capacity and organ regeneration.
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影响因子：
4.6
作者：
Jahangiri, Leila;Sharpe, Michka;Burns, C. Geoffrey
通讯作者：
Burns, C. Geoffrey
影响因子：
48
作者：
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通讯作者：
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影响因子：
64.5
作者：
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通讯作者：
Kuehn, Bernhard
DOI：
10.1152/ajpheart.00514.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Banerjee, Indroneal;Fuseler, John W.;Baudino, Troy A.
通讯作者：
Baudino, Troy A.
影响因子：
64.5
作者：
Alkass, Kanar;Panula, Joni;Bergmann, Olaf
通讯作者：
Bergmann, Olaf