title: Primitive erythropoiesis is regulated by miR-126 via nonhematopoietic Vcam-1+ cells.
abstract: Primitive erythropoiesis defines the onset of hematopoiesis in the yolk sac of the early embryo and is initiated by the emergence of progenitors assayed as colony-forming cells (EryP-CFCs). EryP-CFCs are detected for only a narrow window during embryonic development, suggesting that both their initiation and termination are tightly controlled. Using the embryonic stem differentiation system to model primitive erythropoiesis, we found that miR-126 regulates the termination of EryP-CFC development. Analyses of miR-126 null embryos revealed that this miR also regulates EryP-CFCs in vivo. We identified vascular cell adhesion molecule-1 (Vcam-1) expressed by a mesenchymal cell population as a relevant target of miR-126. Interaction of EryP-CFCs with Vcam-1 accelerated their maturation to ßh1-globin(+) and Ter119(+) cells through a Src family kinase. These findings uncover a cell nonautonomous regulatory pathway for primitive erythropoiesis that may provide insight into the mechanism(s) controlling the developmental switch from primitive to definitive hematopoiesis.
authors: McEwen Centre for Regenerative Medicine, University Health Network, Toronto, ON, Canada.
authors: Christopher M
authors: CM
authors: Sturgeon
authors: Laurie
authors: L
authors: Chicha
authors: Andrea
authors: A
authors: Ditadi
authors: Qinbo
authors: Q
authors: Zhou
authors: Kathleen E
authors: KE
authors: McGrath
authors: James
authors: J
authors: Palis
authors: Scott M
authors: SM
authors: Hammond
authors: Shusheng
authors: S
authors: Wang
authors: Eric N
authors: EN
authors: Olson
authors: Gordon
authors: G
authors: Keller
mesh_terms: D000818:Animals; D002460:Cell Line; D018920:Coculture Techniques; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000502:physiology; D004900:Erythroblasts / Q000166:cytology / Q000502:physiology; D015672:Erythroid Precursor Cells / Q000166:cytology* / Q000502:physiology; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism / Q000502:physiology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: C545201:MIRN126 microRNA, mouse; D035683:MicroRNAs; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2