Tie1, a receptor tyrosine kinase essential for vascular endothelial cell integrity, is not critical for the development of hematopoietic cells.
The receptor tyrosine kinase Tie1 is expressed in both vascular endothelial cells and immature hematopoietic cells. Expression of a common signaling molecule in distinct cellular lineages may suggest common ancestry of these lineages in ontogeny and/or utilization of shared signaling pathways. Tie 1-deficient mice carrying a targeted insertional mutation in germ line show defects in endothelial cell integrity resulting in edema and hemorrhage. To analyse the potential role of this kinase in hematopoietic cells, we have now compared hematopoietic compartments in wildtype and Tiel-deficient mice. The results show: (1) Total cellularity is mildly reduced comparing Tie1-/- and wildtype fetal liver from day 15.5 of gestation. (2) In vitro colony assays and cell transfer experiments of fetal liver cells into lymphocyte-deficient recombination-activating-gene-2-/- mice reveal that Tie1-/- hematopoietic progenitor cells can generate myeloid lineages as well as T and B lymphocytes. (3) Tie1-/- fetal liver cells contain long-term (at least 4 months) bone marrow-reconstituting hematopoietic stem cells suggesting that this kinase is not critical for stem cell-engraftment nor self-renewal.
Rodewald
H R
HR
Basel Institute for Immunology, Switzerland.
Sato
T N
TN
D000818:Animals; D001483:Base Sequence; D001854:Bone Marrow Cells; D004730:Endothelium, Vascular / Q000166:cytology*; D006410:Hematopoiesis; D006412:Hematopoietic Stem Cells / Q000502:physiology; D007377:Interleukin-3 / Q000494:pharmacology; D008214:Lymphocytes / Q000502:physiology; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D042810:Receptor, TIE-1; D042764:Receptors, TIE; D019089:Stem Cell Factor / Q000494:pharmacology
D007377:Interleukin-3; D019089:Stem Cell Factor; D016173:Macrophage Colony-Stimulating Factor; D020794:Receptor Protein-Tyrosine Kinases; D042810:Receptor, TIE-1; D042764:Receptors, TIE