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

V Vedantham, G Galang, M Evangelista… - Circulation …, 2015 - Am Heart Assoc
V Vedantham, G Galang, M Evangelista, RC Deo, D Srivastava
Circulation research, 2015Am Heart Assoc
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 …
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.
Am Heart Assoc