January 27, 2015Circulation Research128 citationsOpen Access
View Full PaperRNA Sequencing of Mouse Sinoatrial Node Reveals an Upstream Regulatory Role for Islet-1 in Cardiac Pacemaker Cells
Key Result
RNA sequencing of mouse sinoatrial node tissue revealed that the pacemaker cell transcriptome diverges sharply from other cardiomyocytes and that Islet-1 is a positive transcriptional regulator.
Structured PICO
P
Population
Mouse sinoatrial node (sinus node reporter mouse line and sinoatrial node tissue lacking Islet-1)
E
Exposure
RNA sequencing and laser capture microdissection to characterize transcriptome; evaluation of Islet-1 deficiency
C
Comparator
Other cardiomyocytes
O
Outcome
Characterization of the transcriptome of pacemaker cells and identification of transcriptional networks (role of Islet-1)surrogate
This study identifies the unique transcriptome of cardiac pacemaker cells and establishes Islet-1 as a key upstream transcriptional regulator, providing foundational knowledge for future regenerative therapies for sinus node disease.
Abstract
RATIONALE: 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). OBJECTIVE: To characterize the transcriptome of PCs using RNA sequencing and to identify transcriptional networks responsible for PC gene expression. METHODS AND RESULTS: We used laser capture microdissection on a sinus node reporter mouse line to isolate RNA from PCs for RNA sequencing. Differential expression and network analysis identified novel sinoatrial node-enriched genes and predicted that the transcription factor Islet-1 is active in developing PCs. RNA sequencing on sinoatrial node tissue lacking Islet-1 established that Islet-1 is an important transcriptional regulator within the developing sinoatrial node. CONCLUSIONS: (1) The PC transcriptome diverges sharply from other cardiomyocytes; (2) Islet-1 is a positive transcriptional regulator of the PC gene expression program.
Cite This Study
Vedantham et al. (Tue,) conducted a other in Sinus node disease. Islet-1 deficiency vs. Normal Islet-1 expression was evaluated on Transcriptome characterization and transcriptional network identification. RNA sequencing of mouse sinoatrial node tissue revealed that the pacemaker cell transcriptome diverges sharply from other cardiomyocytes and that Islet-1 is a positive transcriptional regulator.