Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration.
Frequency of mononuclear diploid cardiomyocytes underlies natural variation in heart regeneration.
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DOI：
10.1038/ng.3929
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发表时间：
2017-09
期刊：
影响因子：
30.8
通讯作者：
Sucov HM
中科院分区：
文献类型：
--
作者：
Patterson M;Barske L;Van Handel B;Rau CD;Gan P;Sharma A;Parikh S;Denholtz M;Huang Y;Yamaguchi Y;Shen H;Allayee H;Crump JG;Force TI;Lien CL;Makita T;Lusis AJ;Kumar SR;Sucov HM
成年哺乳动物心肌细胞损伤后的再生被认为是最小的。单核细胞二倍体心肌细胞（MNDCMs），一个相对较小的亚群在成人心脏，可以解释所观察到的再生程度，但这还没有得到测试。我们调查了120个近交系小鼠品系，发现成年单核心肌细胞的频率变化惊人（>7倍）。冠脉结扎后心肌细胞增殖和心功能恢复均与损伤前MNDCM含量相关。使用全基因组关联，我们将Tnni3k鉴定为影响该组合物变化的一个基因，并证明Tnni3k敲除导致损伤后MNDCM含量升高和心肌细胞增殖增加。反过来，在斑马鱼中过表达Tnni3k促进心肌细胞多倍化和心脏再生受损。我们的研究结果证实了MNDCMs在心脏再生中的相关性。此外，它们意味着内在心脏再生在所有个体中既不有限也不统一，而是受多个基因影响的可变特征。
Adult mammalian cardiomyocyte regeneration after injury is thought to be minimal. Mononuclear diploid cardiomyocytes (MNDCMs), a relatively small subpopulation in the adult heart, may account for the observed degree of regeneration, but this has not been tested. We surveyed 120 inbred mouse strains and found that the frequency of adult mononuclear cardiomyocytes was surprisingly variable (>7-fold). Cardiomyocyte proliferation and heart functional recovery after coronary artery ligation both correlated with pre-injury MNDCM content. Using genome-wide association, we identified Tnni3k as one gene that influences variation in this composition and demonstrated that Tnni3k knockout resulted in elevated MNDCM content and increased cardiomyocyte proliferation after injury. Reciprocally, overexpression of Tnni3k in zebrafish promoted cardiomyocyte polyploidization and compromised heart regeneration. Our results corroborate the relevance of MNDCMs in heart regeneration. Moreover, they imply that intrinsic heart regeneration is not limited nor uniform in all individuals, but rather is a variable trait influenced by multiple genes.
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影响因子：
3.7
作者：
Fukata M;Ishikawa F;Najima Y;Yamauchi T;Saito Y;Takenaka K;Miyawaki K;Shimazu H;Shimoda K;Kanemaru T;Nakamura K;Odashiro K;Nagafuji K;Harada M;Akashi K
通讯作者：
Akashi K
影响因子：
64.5
作者：
Bersell, Kevin;Arab, Shima;Kuehn, Bernhard
通讯作者：
Kuehn, Bernhard
影响因子：
21.3
作者：
D'Uva, Gabriele;Aharonov, Alla;Tzahor, Eldad
通讯作者：
Tzahor, Eldad
影响因子：
4.5
作者：
Lodder EM;Scicluna BP;Milano A;Sun AY;Tang H;Remme CA;Moerland PD;Tanck MW;Pitt GS;Marchuk DA;Bezzina CR
通讯作者：
Bezzina CR
DOI：
10.1073/pnas.1408233111
发表时间：
2014-06-17
影响因子：
11.1
作者：
Ali, Shah R.;Hippenmeyer, Simon;Ardehali, Reza
通讯作者：
Ardehali, Reza