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)