Expression analysis of Baf60c during heart regeneration in axolotls and neonatal mice
Expression analysis of Baf60c during heart regeneration in axolotls and neonatal mice
复制标题
DOI：
10.1111/dgd.12281
复制
发表时间：
2016-04
期刊：
影响因子：
4.6
通讯作者：
Ryo Nakamura;Kazuko Koshiba-Takeuchi;Megumi Tsuchiya;Mizuyo Kojima;Asuka Miyazawa;Kohei Ito;Hidesato Ogawa;J. Takeuchi
中科院分区：
文献类型：
--
作者：
Ryo Nakamura;Kazuko Koshiba-Takeuchi;Megumi Tsuchiya;Mizuyo Kojima;Asuka Miyazawa;Kohei Ito;Hidesato Ogawa;J. Takeuchi
一些生物，如斑马鱼、尾鱼两栖动物和新生小鼠，在受伤后具有心脏再生的能力。然而，成年哺乳动物无法再生它们的心脏。为了了解新生小鼠为什么能再生心脏，我们重点研究了表观遗传因素，这些因素参与了许多组织中的细胞分化。BAF60c(BRG1/BRM相关因子60c)是ATP依赖的染色质重塑复合体的一个组成部分，在心脏发育早期对心肌细胞的分化起着至关重要的作用。为了研究BAF60c在出生后心脏动态平衡和再生中的作用，我们研究了BAF60c在小鼠和Axolotls中的详细表达/定位模式。在小鼠心脏发育早期，BAF60c在整个心脏中高度表达，但在出生后逐渐下调。在新生小鼠和轴突的心脏再生过程中，BAF60c的表达在切除后强烈上调。有趣的是，切除后BAF60c上调的时间与心肌细胞增殖的时间动力学一致。此外，BAF60c基因敲除可抑制新生小鼠心肌细胞的增殖。这些数据表明，BAF60c在心脏发育和再生过程中对心肌细胞的增殖起重要作用。这是第一个表明BAF60c有助于脊椎动物心脏再生的研究。
Some organisms, such as zebrafish, urodele amphibians, and newborn mice, have a capacity for heart regeneration following injury. However, adult mammals fail to regenerate their hearts. To know why newborn mice can regenerate their hearts, we focused on epigenetic factors, which are involved in cell differentiation in many tissues. Baf60c (BRG1/BRM‐associated factor 60c), a component of ATP‐dependent chromatin‐remodeling complexes, has an essential role for cardiomyocyte differentiation at the early heart development. To address the function of Baf60c in postnatal heart homeostasis and regeneration, we examined the detailed expression/localization patterns of Baf60c in both mice and axolotls. In the mouse heart development, Baf60c was highly expressed in the entire heart at the early stages, but gradually downregulated at the postnatal stages. During heart regeneration in neonatal mice and axolotls, Baf60c expression was strongly upregulated after resection. Interestingly, the timing of Baf60c upregulation after resection was consistent with the temporal dynamics of cardiomyocyte proliferation. Moreover, knockdown of Baf60c downregulated proliferation of neonatal mouse cardiomyocytes. These data suggested that Baf60c plays an important role in cardiomyocyte proliferation in heart development and regeneration. This is the first study indicating that Baf60c contributes to the heart regeneration in vertebrates.