title: β(2)-Integrin and Notch-1 differentially regulate CD34(+)CD31(+) cell plasticity in vascular niches.
abstract: OBJECTIVE
  The implication of circulating haematopoietic CD34(+) progenitors in the vasculature is unclear due to the lack of understanding of their characteristics and plasticity mediated by their cellular microenvironment. We investigated how vascular smooth muscle cells (SMCs) and their interactions with endothelial cells (ECs) affect the behaviour and plasticity of CD34(+)CD31(+) progenitors and the underlying mechanisms.
  
  
  RESULTS
  Human peripheral blood-derived CD34(+)CD31(+) cells were directly transplanted into injured arteries in vivo and co-cultured with ECs and SMCs in vitro. CD34(+)CD31(+) progenitors injected into wire-injured mouse arteries differentiate into ECs and macrophages in the neoendothelial layer and neointima, respectively. SMC-co-culture increases CD34(+)CD31(+) cell mobility and adhesion to and transmigration across ECs. Sorted CD34(+)CD31(+) progenitors that adhered to ECs co-cultured with SMCs have the capacity to form capillary-like structures in Matrigel and chimeric blood vessels in vivo. Sorted transmigrated progenitors give rise to macrophages with increased pro-angiogenic activity. These differentiations of CD34(+)CD31(+) progenitors into ECs and macrophages are mediated by β(2)-integrin and Notch-1, respectively. β(2)-Integrin and Notch-1 are activated by their counterligands, intercellular adhesion molecule-1 (ICAM-1) and jagged-1, which are highly expressed in the neoendothelium and neointima in injured arteries. Intra-arterial injection of β(2)-integrin-activated CD34(+)CD31(+) progenitors into wire-injured mouse arteries inhibits neointima formation.
  
  
  CONCLUSIONS
  Our findings indicate that the peripheral vascular niches composed of ECs and SMCs may predispose haematopoietic CD34(+)CD31(+) progenitors to differentiate into ECs and macrophages through the activations of the ICAM-1/β(2)-integrin and jagged-1/Notch-1 cascades, respectively.
authors.affiliation: Institute of Cellular and System Medicine,  National Health Research Institutes, Miaoli 350,  Taiwan.
authors.forename: Yu-Tsung
authors.initials: YT
authors.lastname: Shih
authors.forename: Mei-Cun
authors.initials: MC
authors.lastname: Wang
authors.forename: Tung-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Ding-Yu
authors.initials: DY
authors.lastname: Lee
authors.forename: Pei-Ling
authors.initials: PL
authors.lastname: Lee
authors.forename: Shaw-Fang
authors.initials: SF
authors.lastname: Yet
authors.forename: Jeng-Jiann
authors.initials: JJ
authors.lastname: Chiu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D018821:CD18 Antigens / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002448:Cell Adhesion; D002465:Cell Movement; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D005263:Femoral Artery / Q000293:injuries; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D000072100:Jagged-1 Protein; D008264:Macrophages / Q000166:cytology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D058426:Neointima / Q000517:prevention & control; D018919:Neovascularization, Physiologic; D051881:Receptor, Notch1 / Q000378:metabolism*; D000072099:Serrate-Jagged Proteins; D057705:Transendothelial and Transepithelial Migration
chemical_list: D001057:Apolipoproteins E; D018821:CD18 Antigens; D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497762:Notch1 protein, mouse; D051881:Receptor, Notch1; D000072099:Serrate-Jagged Proteins; D018799:Intercellular Adhesion Molecule-1