title: Hematopoietic progenitors are required for proper development of coronary vasculature.
abstract: BACKGROUND
  During embryogenesis, hematopoietic cells appear in the myocardium prior to the initiation of coronary formation. However, their role is unknown.
  
  
  OBJECTIVE
  Here we investigate whether pre-existing hematopoietic cells are required for the formation of coronary vasculature.
  
  
  RESULTS
  As a model of for hematopoietic cell deficient animals, we used Runx1 knockout embryos and Vav1-cre; R26-DTA embryos, latter of which genetically ablates 2/3 of CD45(+) hematopoietic cells. Both Runx1 knockout embryos and Vav1-cre; R26-DTA embryos revealed disorganized, hypoplastic microvasculature of coronary vessels on section and whole-mount stainings. Furthermore, coronary explant experiments showed that the mouse heart explants from Runx1 and Vav1-cre; R26-DTA embryos exhibited impaired coronary formation ex vivo. Interestingly, in both models it appears that epicardial to mesenchymal transition is adversely affected in the absence of hematopoietic progenitors.
  
  
  CONCLUSIONS
  Hematopoietic cells are not merely passively transported via coronary vessel, but substantially involved in the induction of the coronary growth. Our findings suggest a novel mechanism of coronary growth.
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Department of Medicine, Section of Cardiology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Gentian
authors.initials: G
authors.lastname: Lluri
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Huang
authors.affiliation: Children's Discovery and Innovation Institute Department of Pediatrics, Department of Molecular Cell and Integrative Physiology, David Geffen School of Medicine, USA.
authors.forename: Marlin
authors.initials: M
authors.lastname: Touma
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Harmon
authors.affiliation: Department of Molecular Cell and Developmental Biology, University of California, Los Angeles, Los Angeles, CA 90095, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA 90095, USA; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA 90095, USA. Electronic address: anakano@ucla.edu.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakano
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D019070:Cell Lineage / Q000235:genetics; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics; D003331:Coronary Vessels / Q000196:embryology / Q000254:growth & development* / Q000378:metabolism; D004622:Embryo, Mammalian; D047108:Embryonic Development / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006321:Heart / Q000254:growth & development*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C493726:Runx1 protein, mouse
keywords: Cardiac development; Coronary formation; EMT; Epicardium; Hematopoietic progenitors