Ezh2 is not required for cardiac regeneration in neonatal mice.
Ezh2 is not required for cardiac regeneration in neonatal mice.
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DOI：
10.1371/journal.pone.0192238
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Delgado-Olguin P
中科院分区：
文献类型：
--
作者：
Ahmed A;Wang T;Delgado-Olguin P
新生小鼠的心脏在生命的第一周内具有显著的再生失去的心肌的能力。新生儿心肌细胞在损伤后重新表达控制细胞增殖的胎儿基因，以促进再生。出生一周后心脏再生能力的丧失与胎儿转录程序的抑制相一致，该转录程序是由表观遗传调节因子协调的。zeste同源物2的组蛋白甲基转移酶增强子（Ezh2）是胎儿心脏转录程序的抑制因子，可抑制心肌细胞增殖，提示其在心脏再生中具有潜在功能。然而，最近的研究表明，Ezh2对于新生儿心脏再生是必不可少的。在这里，我们提供了支持这一发现的证据，并证明Ezh2缺乏不影响新生儿心脏的再生。我们在胚胎心肌细胞分化过程中灭活Ezh2，导致赖氨酸27位点三甲基化的组蛋白H3 （H3K27me3）缺失。心肌细胞缺乏Ezh2不影响心肌梗死（MI）和心肌损伤根尖切除模型在出生后第1天（P1）纤维化瘢痕的清除。同样，心肌细胞特异性Ezh2的缺失并不影响心肌梗死或P7根尖切除后纤维化疤痕的大小，这表明它不会延长再生时间窗口。我们的研究结果表明，先天性新生儿心脏再生不需要Ezh2。
The neonatal mouse heart has the remarkable capacity to regenerate lost myocardium within the first week of life. Neonatal cardiomyocytes re-express fetal genes that control cell proliferation after injury to promote regeneration. The loss of regenerative capacity of the heart one week after birth coincides with repression of a fetal transcriptional program coordinated by epigenetic regulators. The histone methyltransferase enhancer of zeste homolog 2 (Ezh2) is a repressor of fetal cardiac transcriptional programs and suppresses cardiomyocyte cell proliferation, suggesting a potential function in heart regeneration. However, it was recently demonstrated that Ezh2 is dispensable for heart regeneration in the neonatal heart. Here, we provide evidence supporting this finding and demonstrate that Ezh2 deficiency does not affect regeneration of the neonatal heart. We inactivated Ezh2 in differentiating embryonic cardiomyocytes, which led to depletion of histone H3 trimethylated at lysine 27 (H3K27me3). Ezh2 deficiency in cardiomyocytes did not affect clearance of the fibrotic scar in myocardial infarction (MI) and apical resection models of cardiac injury at post-natal day 1 (P1). Similarly, cardiomyocyte-specific loss of Ezh2 did not affect fibrotic scar size after MI or apical resection at P7, suggesting that it does not extend the regenerative time window. Our results demonstrate that Ezh2 is not required for innate neonatal cardiac regeneration.
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DOI：
10.1073/pnas.1208863110
发表时间：
2013-01-02
影响因子：
11.1
作者：
Porrello, Enzo R.;Mahmoud, Ahmed I.;Sadek, Hesham A.
通讯作者：
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影响因子：
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DOI：
10.1073/pnas.1214608110
发表时间：
2013-01-22
影响因子：
11.1
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DOI：
10.1073/pnas.042390499
发表时间：
2002-03-05
影响因子：
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作者：
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