title: RNA sequencing of mouse sinoatrial node reveals an upstream regulatory role for Islet-1 in cardiac pacemaker cells.
abstract: BACKGROUND
  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.
  
  
  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.
authors.affiliation: 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.
authors.forename: Vasanth
authors.initials: V
authors.lastname: Vedantham
authors.affiliation: 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.
authors.forename: Giselle
authors.initials: G
authors.lastname: Galang
authors.affiliation: 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.
authors.forename: Melissa
authors.initials: M
authors.lastname: Evangelista
authors.affiliation: 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.
authors.forename: Rahul C
authors.initials: RC
authors.lastname: Deo
authors.affiliation: 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.
authors.forename: Deepak
authors.initials: D
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D005260:Female; D005318:Fetal Heart / Q000166:cytology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D017930:Genes, Reporter; D006325:Heart Atria / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D060850:LIM-Homeodomain Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D061346:Laser Capture Microdissection; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D012849:Sinoatrial Node / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D013382:Subtraction Technique; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D060850:LIM-Homeodomain Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C063843:insulin gene enhancer binding protein Isl-1
keywords: Hcn4 protein, mouse; Isl1 protein, mouse; high-throughput RNA sequencing; laser capture microdissection; sinoatrial node; transcription factors