Identification of cardiac hemo-vascular precursors and their requirement of sphingosine-1-phosphate receptor 1 for heart development.
The cardiac endothelium plays a crucial role in the development of a functional heart. However, the precise identification of the endocardial precursors and the mechanisms they require for their role in heart morphogenesis are not well understood. Using in vivo and in vitro cell fate tracing concomitant with specific cell ablation and embryonic heart transplantation studies, we identified a unique set of precursors which possess hemogenic functions and express the stem cell leukemia (SCL) gene driven by its 5' enhancer. These hemo-vascular precursors give rise to the endocardium, atrioventricular cushions and coronary vascular endothelium. Furthermore, deletion of the sphingosine-1-phosphate receptor 1 (S1P1) in these precursors leads to ventricular non-compaction cardiomyopathy, a poorly understood condition leading to heart failure and early mortality. Thus, we identified a distinctive population of hemo-vascular precursors which require S1P1 to exert their functions and are essential for cardiac morphogenesis.
Department of Pediatrics and Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
Yan
Y
Hu
Department of Pediatrics and Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
Brian C
BC
Belyea
Department of Pediatrics and Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
Minghong
M
Li
Department of Hematology, West German Cancer Center, University Hospital Essen, Essen, Germany.
Joachim R
JR
Göthert
Department of Pediatrics and Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
R Ariel
RA
Gomez
Department of Pediatrics and Department of Biology, University of Virginia, Charlottesville, Virginia, USA.
Maria Luisa S
ML
Sequeira-Lopez
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000235:genetics*; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology* / Q000196:embryology / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D006321:Heart / Q000196:embryology*; D056830:Isolated Noncompaction of the Ventricular Myocardium / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D009024:Morphogenesis; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism*; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1 / Q000235:genetics / Q000378:metabolism
D049349:Receptors, Lysosphingolipid; D000073942:T-Cell Acute Lymphocytic Leukemia Protein 1; C489366:Tal1 protein, mouse