RNA Sequencing of Mouse Sinoatrial Node Reveals an Upstream Regulatory Role for Islet-1 in Cardiac Pacemaker Cells

Vedantham, Vasanth; Galang, Giselle; Evangelista, Melissa; Deo, Rahul C.; Srivastava, Deepak

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RNA Sequencing of Mouse Sinoatrial Node Reveals an Upstream Regulatory Role for Islet-1 in Cardiac Pacemaker Cells

Published Date:

Jan 26 2015

Source:

Circ Res. 116(5):797-803.

Language:

English

[PDF-961.36 KB]

Details:

Personal Authors:

Vedantham, Vasanth ; Galang, Giselle ; Evangelista, Melissa ; Deo, Rahul C. ; Srivastava, Deepak ;

Keywords:

[+]

Pubmed ID:

25623957

Pubmed Central ID:

PMC4344860

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.

Document Type:

Journal Article

Collection(s):

CDC Public Access

Funding:

P01 HL089707/HL/NHLBI NIH HHS/United States
U01 HL098179/HL/NHLBI NIH HHS/United States
DP2 HL123228/DP/NCCDPHP CDC HHS/United States
K08 HL101989/HL/NHLBI NIH HHS/United States
U01 HL100406/HL/NHLBI NIH HHS/United States
R01 HL057181/HL/NHLBI NIH HHS/United States
U01 HL107440-03/HL/NHLBI NIH HHS/United States
K08 HL093861/HL/NHLBI NIH HHS/United States
U01 HL107440/HL/NHLBI NIH HHS/United States
DP2 HL123228/HL/NHLBI NIH HHS/United States

Supporting Files:

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