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

Details

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

  More +
• 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 ; 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
• Volume:
  116
• Issue:
  5
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:0a583f74feb8199441f4c0f9cd2edec81a4cff2e8e1d63ac2970d60dec927f3a
• Download URL:
  https://stacks.cdc.gov/view/cdc/30312/cdc_30312_DS1.pdf
• File Type:
  [PDF - 961.36 KB ]