In vitro hematopoietic and endothelial potential of flk-1(-/-) embryonic stem cells and embryos

Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2159-64. doi: 10.1073/pnas.96.5.2159.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion
  • Cells, Cultured
  • Embryo, Mammalian
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / physiology*
  • Flow Cytometry
  • Gene Expression Regulation, Developmental*
  • Hematopoietic Stem Cells / cytology
  • Hematopoietic Stem Cells / physiology*
  • Mice
  • Mice, Knockout
  • Receptor Protein-Tyrosine Kinases / deficiency
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Receptors, Growth Factor / deficiency
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / physiology*
  • Receptors, Mitogen / physiology
  • Receptors, Vascular Endothelial Growth Factor
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Stem Cells / physiology*

Substances

  • Receptors, Growth Factor
  • Receptors, Mitogen
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Vascular Endothelial Growth Factor