Analysis of human TIE2 function on hematopoietic stem cells in umbilical cord blood.
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.
Yuasa
Hiromi
H
Department of Hamatopoiesis, Institute of Molecular Genetics and Embryology, Kumamoto University, Japan.
Takakura
Nobuyuki
N
Shimomura
Taizou
T
Suenobu
Souichi
S
Yamada
Taketo
T
Nagayama
Hitomi
H
Oike
Yuichi
Y
Suda
Toshio
T
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
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