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RNA Sequencing of Mouse Sinoatrial Node Reveals an Upstream Regulatory Role for Islet-1 in Cardiac Pacemaker Cells
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Jan 26 2015
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Source: Circ Res. 116(5):797-803.
[PDF-961.36 KB]
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Alternative Title:Circ Res
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Description: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 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.
Conclusions
(1) The PC transcriptome diverges sharply from other cardiomyocytes; (2) Isl1 is a positive transcriptional regulator of the PC gene expression program.
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Pubmed ID:25623957
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Pubmed Central ID:PMC4344860
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