RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells.
RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells.
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DOI：
10.1161/circresaha.116.305913
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发表时间：
2015-02-27
影响因子：
20.1
通讯作者：
Srivastava D
中科院分区：
文献类型：
--
作者：
Vedantham V;Galang G;Evangelista M;Deo RC;Srivastava D
用再生或基于细胞的疗法治疗窦房结疾病将需要详细了解心脏起搏细胞（PC）中的基因调控网络。利用RNA测序技术对PC的转录组进行表征，并确定负责PC基因表达的转录网络。我们在窦房结报告小鼠系上使用激光捕获显微切割（LCM）从PC分离RNA用于RNA测序（RNA-Seq）。差异表达和网络分析确定了新的SAN富集基因，并预测转录因子Islet-1（Isl1）在发育中的起搏细胞中是活跃的。对缺乏Isl1的SAN组织的RNA-Seq确定了Isl1是发育中的SAN内的重要转录调节因子。(1)PC基因转录组与其他心肌细胞差异显著;（2）Isl1是PC基因表达程序的正性转录调节因子。
Treatment of sinus node disease with regenerative or cell-based therapies will require a detailed understanding of gene regulatory networks in cardiac pacemaker cells (PCs). To characterize the transcriptome of PCs using RNA sequencing, and to identify transcriptional networks responsible for PC gene expression. We used laser capture micro-dissection (LCM) on a sinus node reporter mouse line to isolate RNA from PCs for RNA sequencing (RNA-Seq). Differential expression and network analysis identified novel SAN-enriched genes, and predicted that the transcription factor Islet-1 (Isl1) is active in developing pacemaker cells. RNA-Seq on SAN tissue lacking Isl1 established that Isl1 is an important transcriptional regulator within the developing SAN. (1) The PC transcriptome diverges sharply from other cardiomyocytes; (2) Isl1 is a positive transcriptional regulator of the PC gene expression program.