Details:

Alternative Title:
Circ Res
Personal Author:
Vedantham, Vasanth ; Galang, Giselle ; Evangelista, Melissa ; Deo, Rahul C. ; Srivastava, Deepak
Vedantham, Vasanth ; Galang, Giselle ; Evangelista, Melissa ; Deo, Rahul C. ; Srivastava, Deepak Less -
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.


Subject:
[+]
Animals
Article
Female
Fetal Heart
Gene Expression Profiling
Gene Expression Regulation, Developmental
Gene Regulatory Networks
Genes, Reporter
Hcn4
Heart Atria
High-Throughput Nucleotide Sequencing
Isl1
Laser Capture Microdissection
LIM-Homeodomain Proteins
Male
Mice
Molecular Sequence Data
Mouse Heart Development
Myocardial Contraction
Myocytes, Cardiac
RNA, Messenger
RNA-Seq
Sinoatrial Node
Subtraction Technique
Transcription, Genetic
Transcription Factors
Transcriptome
Sinoatrial Node
Transcription Factors

Source:
Circ Res. 116(5):797-803.
Pubmed ID:
25623957
Pubmed Central ID:
PMC4344860
Document Type:
Journal Article
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 ; ... More +
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 Less -
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:0a583f74feb8199441f4c0f9cd2edec81a4cff2e8e1d63ac2970d60dec927f3a
File Type:

Supporting Files

• 	nihms658920f4.jpg	jpeg
  	nihms658920.nxml	xml
  	nihms658920f1.gif	gif
  	nihms658920f1.jpg	jpeg
  	nihms658920f2.gif	gif
  	nihms658920f2.jpg	jpeg
  	nihms658920f3.gif	gif
  	nihms658920f3.jpg	jpeg
  	nihms658920f4.gif	gif

More +