Hematopoietic stem cells express Tie-2 receptor in the murine fetal liver.
Tie-2 receptor tyrosine kinase expressed in endothelial and hematopoietic cells is believed to play a role in both angiogenesis and hematopoiesis during development of the mouse embryo. This article addressed whether Tie-2 is expressed on fetal liver hematopoietic stem cells (HSCs) at day 14 of gestation. With the use of anti-Tie-2 monoclonal antibody, its expression was detected in approximately 7% of an HSC population of Kit-positive, Sca-1-positive, lineage-negative or -low, and AA4.1-positive (KSLA) cells. These Tie-2-positive KSLA (T(+) KSLA) cells represent 0.01% to 0.02% of fetal liver cells. In vitro colony and in vivo competitive repopulation assays were performed for T(+) KSLA cells and Tie-2-negative KSLA (T(-) KSLA) cells. In the presence of stem cell factor, interleukin-3, and erythropoietin, 80% of T(+) KSLA cells formed colonies in vitro, compared with 40% of T(-) KSLA cells. Long-term multilineage repopulating cells were detected in T(+) KSLA cells, but not in T(-) KSLA cells. An in vivo limiting dilution analysis revealed that at least 1 of 8 T(+) KSLA cells were such repopulating cells. The successful secondary transplantation initiated with a limited number of T(+) KSLA cells suggests that these cells have self-renewal potential. In addition, engraftment of T(+) KSLA cells in conditioned newborn mice indicates that these HSCs can be adapted equally by the adult and newborn hematopoietic environments. The data suggest that T(+) KSLA cells represent HSCs in the murine fetal liver. (Blood. 2000;96:3757-3762)
Hsu
H C
HC
Department of Immunology, Institute of Basic Medical Sciences, University of Tsukuba, Japan.
Ema
H
H
Osawa
M
M
Nakamura
Y
Y
Suda
T
T
Nakauchi
H
H
D000818:Animals; D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; D001854:Bone Marrow Cells / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D019070:Cell Lineage / Q000187:drug effects; D005260:Female; D005333:Fetus; D006410:Hematopoiesis / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000201:enzymology* / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000196:embryology* / Q000201:enzymology*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010641:Phenotype; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*; D042787:Receptor, TIE-2; D013234:Stem Cells; D018183:Transplantation Chimera
D000911:Antibodies, Monoclonal; D000950:Antigens, Ly; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; D019009:Proto-Oncogene Proteins c-kit; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2