title: Islet1 derivatives in the heart are of both neural crest and second heart field origin.
abstract: BACKGROUND
  Islet1 (Isl1) has been proposed as a marker of cardiac progenitor cells derived from the second heart field and is utilized to identify and purify cardiac progenitors from murine and human specimens for ex vivo expansion. The use of Isl1 as a specific second heart field marker is dependent on its exclusion from other cardiac lineages such as neural crest.
  
  
  OBJECTIVE
  Determine whether Isl1 is expressed by cardiac neural crest.
  
  
  RESULTS
  We used an intersectional fate-mapping system using the RC::FrePe allele, which reports dual Flpe and Cre recombination. Combining Isl1(Cre/+), a SHF driver, and Wnt1::Flpe, a neural crest driver, with Rc::FrePe reveals that some Isl1 derivatives in the cardiac outflow tract derive from Wnt1-expressing neural crest progenitors. In contrast, no overlap was observed between Wnt1-derived neural crest and an alternative second heart field driver, Mef2c-AHF-Cre.
  
  
  CONCLUSIONS
  Isl1 is not restricted to second heart field progenitors in the developing heart but also labels cardiac neural crest. The intersection of Isl1 and Wnt1 lineages within the heart provides a caveat to using Isl1 as an exclusive second heart field cardiac progenitor marker and suggests that some Isl1-expressing progenitor cells derived from embryos, embryonic stem cultures, or induced pluripotent stem cultures may be of neural crest lineage.
authors.affiliation: Department of Cell and Developmental Biology, Cardiovascular Institute and Institute for Regenerative Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, USA.
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Engleka
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Manderfield
authors.forename: Rachael D
authors.initials: RD
authors.lastname: Brust
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Ashley
authors.initials: A
authors.lastname: Cohen
authors.forename: Susan M
authors.initials: SM
authors.lastname: Dymecki
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Epstein
mesh_terms: D000818:Animals; D015415:Biomarkers; D019070:Cell Lineage; D049452:Green Fluorescent Proteins / Q000235:genetics; D006321:Heart / Q000196:embryology*; D060850:LIM-Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009432:Neural Crest / Q000166:cytology / Q000196:embryology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D051155:Wnt1 Protein; C063843:insulin gene enhancer binding protein Isl-1; D049452:Green Fluorescent Proteins