Transcriptional Landscape of Cardiomyocyte Maturation.
Transcriptional Landscape of Cardiomyocyte Maturation.
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心肌细胞成熟的转录景观。
DOI：
10.1016/j.celrep.2015.10.032
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发表时间：
2015-11-24
期刊：
影响因子：
8.8
通讯作者：
Kwon C
中科院分区：
文献类型：
--
作者：
Uosaki H;Cahan P;Lee DI;Wang S;Miyamoto M;Fernandez L;Kass DA;Kwon C
几十年来，发育心脏病学的进展提高了我们对心脏发育早期方面的理解，包括心肌细胞（CM）分化。然而，CM成熟的控制，随后需要产生成年肌细胞，仍然是难以捉摸的。在这里，我们分析了200多个从早期胚胎到成年心脏的微阵列数据集，并发现了大量在成熟过程中表达逐渐持续变化的基因。我们生成了一个整合基因表达、生物学途径、转录调控因子和基因调控网络（grn）的图谱，其中显示了在CM成熟过程中激活或抑制的关键转录调控因子和途径的离散集。我们开发了一个基于grn的程序，名为MatStatCM，用于索引CM的成熟状态。MatStatCM表明，多能干细胞衍生的CMs在培养早期成熟，但在胚胎后期由于关键转录因子的异常调节而被阻止。我们的研究为理解CM成熟度提供了基础。
Decades of progress in developmental cardiology has advanced our understanding of the early aspects of heart development, including cardiomyocyte (CM) differentiation. However, control of CM maturation which is subsequently required to generate adult myocytes, remains elusive. Here, we analyzed over 200 microarray datasets from early embryonic to adult hearts and identified a large number of genes whose expression shifts gradually and continuously during maturation. We generated an atlas of integrated gene expression, biological pathways, transcriptional regulators, and gene regulatory networks (GRNs), which show discrete sets of key transcriptional regulators and pathways activated or suppressed during CM maturation. We developed a GRN-based program named MatStatCM that indexes CM maturation status. MatStatCM reveals that pluripotent stem cell-derived CMs mature early in culture, but are arrested at the late embryonic stage with aberrant regulation of key transcription factors. Our study provides a foundation for understanding CM maturation.