Expression and function of murine receptor tyrosine kinases, TIE and TEK, in hematopoietic stem cells.
Two highly related receptor tyrosine kinases, TIE and TEK, comprise a family of endothelial cell-specific kinase. We established monoclonal antibodies against them and performed detailed analyses on their expression and function in murine hematopoietic stem cells (HSCs). TIE and TEK were expressed on 23.7% and 33.3% of lineage marker-negative, c-Kit+ and Sca-1+ (Lin- c-Kit+ Sca-1+) HSCs that contain the majority of day-12 colony-forming units-spleen (CFU-S) and long-term reconstituting cells, but not committed progenitor cells. Lin- c-Kit+ Sca-1+ cells were further divided by the expression of TIE and TEK. TIE+ and TEK+ HSCs as well as each negative counterpart contained high proliferative potential colony-forming cells and differentiated into lymphoid and myeloid progenies both in vitro and in vivo. However, day-12 CFU-S were enriched in TIE+ and TEK+ HSCs. Our findings define TIE and TEK as novel stem cell marker antigens that segregate day-12 CFU-S, and provide evidence of novel signaling pathways that are involved in the functional regulation of HSCs at a specific stage of differentiation, particularly of day-12 CFU-S.
Yano
M
M
Department of Cell Differentiation, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University School of Medicine, Japan.
Iwama
A
A
Nishio
H
H
Suda
J
J
Takada
G
G
Suda
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001853:Bone Marrow; D019556:COS Cells; D002454:Cell Differentiation; D002460:Cell Line; D003114:Colony-Forming Units Assay; D004790:Enzyme Induction; D006412:Hematopoietic Stem Cells / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000235:genetics / Q000276:immunology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D042787:Receptor, TIE-2; D042764:Receptors, TIE; D011993:Recombinant Fusion Proteins / Q000276:immunology; D015398:Signal Transduction
D000911:Antibodies, Monoclonal; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D042764:Receptors, TIE