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Circ Res. 2015 Feb 27;116(5):797-803. doi: 10.1161/CIRCRESAHA.116.305913. Epub 2015 Jan 26.

RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells.

Author information

1
From the Gladstone Institute of Cardiovascular Disease, San Francisco, CA (V.V., G.G., M.E., D.S.); and Division of Cardiology, Departments of Medicine (V.V., G.G., R.C.D.), Pediatrics (D.S.), and Biochemistry and Biophysics (R.C.D., D.S.), Institute for Human Genetics, California Institute for Quantitative Biosciences (R.C.D.), and Cardiovascular Research Institute (V.V., G.G., M.E., R.C.D.), University of California, San Francisco.
2
From the Gladstone Institute of Cardiovascular Disease, San Francisco, CA (V.V., G.G., M.E., D.S.); and Division of Cardiology, Departments of Medicine (V.V., G.G., R.C.D.), Pediatrics (D.S.), and Biochemistry and Biophysics (R.C.D., D.S.), Institute for Human Genetics, California Institute for Quantitative Biosciences (R.C.D.), and Cardiovascular Research Institute (V.V., G.G., M.E., R.C.D.), University of California, San Francisco. Vasanth.Vedantham@ucsf.edu Rahul.Deo@ucsf.edu.

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.

KEYWORDS:

Hcn4 protein, mouse; Isl1 protein, mouse; high-throughput RNA sequencing; laser capture microdissection; sinoatrial node; transcription factors

PMID:
25623957
PMCID:
PMC4344860
DOI:
10.1161/CIRCRESAHA.116.305913
[Indexed for MEDLINE]
Free PMC Article

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