title: Analysis of human TIE2 function on hematopoietic stem cells in umbilical cord blood.
abstract: To investigate the behavior of hematopoietic stem cells (HSCs) in cord blood (CB), we analyzed the expression and function of TIE2, a tyrosine kinase receptor. A subpopulation of Lineage (Lin)(-/low)CD34(+) cells in CB expressed TIE2 (18.8%). Assays for long-term culture-initiating cells (LTC-IC) and cobble-stone formation revealed that Lin(-/low)CD34(+)TIE2(+) cells showed to have a capacity of primitive hematopoietic precursor cells in vitro. When Lin(-/low)CD34(+)TIE2(+) cells were cultured on the stromal cells, they transmigrated under the stromal layers and kept an immature character for a few weeks. By contrast, Lin(-/low)CD34(+)TIE2(-) cells differentiated immediately within a few weeks. Finally, we confirmed that 1x10(4)Lin(-/low)CD34(+)TIE2(+) cells were engrafted in non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice, while 1x10(4)Lin(-/low)CD34(+)TIE2(-) cells were not. Taken together, we conclude that TIE2 is a marker of HSCs in CB. A ligand for TIE2, Ang-1 promoted the adhesion of sorted primary Lin(-/low)CD34(+)TIE2(+) cells to fibronectin (FN), and this adhesion may play a critical role in keeping HSCs in an immature status under the stromal cells.
authors.affiliation: Department of Hamatopoiesis, Institute of Molecular Genetics and Embryology, Kumamoto University, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yuasa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Takakura
authors.forename: Taizou
authors.initials: T
authors.lastname: Shimomura
authors.forename: Souichi
authors.initials: S
authors.lastname: Suenobu
authors.forename: Taketo
authors.initials: T
authors.lastname: Yamada
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nagayama
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Oike
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D042683:Angiopoietin-1; D000818:Animals; D018952:Antigens, CD34 / Q000097:blood; D015415:Biomarkers; D002448:Cell Adhesion; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000145:classification / Q000201:enzymology* / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007231:Infant, Newborn; D008024:Ligands; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011247:Pregnancy; D020794:Receptor Protein-Tyrosine Kinases / Q000097:blood*; D042787:Receptor, TIE-2; D014183:Transplantation, Heterologous
chemical_list: C467630:ANGPT1 protein, human; D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; C467628:Angpt1 protein, mouse; D018952:Antigens, CD34; D015415:Biomarkers; D008024:Ligands; D008562:Membrane Glycoproteins; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2