In vitro hematopoietic and endothelial potential of flk-1(-/-) embryonic stem cells and embryos.
Mice deficient in the Flk-1 receptor tyrosine kinase are known to die in utero because of defective vascular and hematopoietic development. Here, we show that flk-1(-/-) embryonic stem cells are nevertheless able to differentiate into hematopoietic and endothelial cells in vitro, although they give rise to a greatly reduced number of blast colonies, a measure of hemangioblast potential. Furthermore, normal numbers of hematopoietic progenitors are found in 7.5-day postcoitum flk-1(-/-) embryos, even though 8. 5-day postcoitum flk-1(-/-) embryos are known to be deficient in such cells. Our results suggest that hematopoietic/endothelial progenitors arise independently of Flk-1, but that their subsequent migration and expansion require a Flk-1-mediated signal.
Department of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada M5G 2C4.
A C
AC
Schuh
P
P
Faloon
Q L
QL
Hu
M
M
Bhimani
K
K
Choi
D000818:Animals; D002448:Cell Adhesion; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D020794:Receptor Protein-Tyrosine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011975:Receptors, Mitogen / Q000502:physiology; D040262:Receptors, Vascular Endothelial Growth Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology*
D017978:Receptors, Growth Factor; D011975:Receptors, Mitogen; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor