title: Myocardial Notch signaling reprograms cardiomyocytes to a conduction-like phenotype.
abstract: BACKGROUND
  Notch signaling has previously been shown to play an essential role in regulating cell fate decisions and differentiation during cardiogenesis in many systems including Drosophila, Xenopus, and mammals. We hypothesized that Notch may also be involved in directing the progressive lineage restriction of cardiomyocytes into specialized conduction cells.
  
  
  RESULTS
  In hearts where Notch signaling is activated within the myocardium from early development onward, Notch promotes a conduction-like phenotype based on ectopic expression of conduction system-specific genes and cell autonomous changes in electrophysiology. With the use of an in vitro assay to activate Notch in newborn cardiomyocytes, we observed global changes in the transcriptome, and in action potential characteristics, consistent with reprogramming to a conduction-like phenotype.
  
  
  CONCLUSIONS
  Notch can instruct the differentiation of chamber cardiac progenitors into specialized conduction-like cells. Plasticity remains in late-stage cardiomyocytes, which has potential implications for engineering of specialized cardiovascular tissues.
authors: Cardiovascular Institute, University of Pennsylvania, 421 Curie Blvd, Philadelphia, PA 19104, USA. srentsch@dom.wustl.edu
authors: Stacey
authors: S
authors: Rentschler
authors: Alberta H
authors: AH
authors: Yen
authors: Jia
authors: J
authors: Lu
authors: Nataliya B
authors: NB
authors: Petrenko
authors: Min Min
authors: MM
authors: Lu
authors: Lauren J
authors: LJ
authors: Manderfield
authors: Vickas V
authors: VV
authors: Patel
authors: Glenn I
authors: GI
authors: Fishman
authors: Jonathan A
authors: JA
authors: Epstein
mesh_terms: D000200:Action Potentials; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001283:Atrioventricular Node / Q000166:cytology*; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics; D019070:Cell Lineage; D058969:Contactin 2 / Q000096:biosynthesis / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D051379:Mice; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000648:ultrastructure; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques; D010641:Phenotype; D011690:Purkinje Fibers / Q000166:cytology; D051881:Receptor, Notch1 / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D015222:Sodium Channels / Q000096:biosynthesis / Q000235:genetics; D020825:T-Box Domain Proteins / Q000096:biosynthesis / Q000235:genetics; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D058969:Contactin 2; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D051881:Receptor, Notch1; D011993:Recombinant Fusion Proteins; D015222:Sodium Channels; D020825:T-Box Domain Proteins; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; C548675:Cntn2 protein, mouse; C489734:Hes1 protein, mouse; C484469:Nkx2-5 protein, mouse; C497762:Notch1 protein, mouse; C568321:Scn5a protein, mouse; C491460:Tbx3 protein, mouse