Published online before print March 17, 2005, doi: 10.1161/01.ATV.0000163182.73190.f9
© 2005 American Heart Association, Inc.
Vascular Biology |
Fibroblast Growth Factor Receptor-1 Expression Is Required for Hematopoietic but not Endothelial Cell Development
From the Department of Genetics and Pathology (P.U.M., P.C., L.J., A.D., L.C.-W.), Rudbeck Laboratory, Uppsala University, Uppsala, Sweden; the Unit of General Pathology and Immunology (R.R., P.D.E.), Department of Biomedical Sciences and Biotechnology, University of Brescia, Brescia, Italy; and the Institute of Biotechnology (J.P.), University of Helsinki, Helsinki, Finland
Correspondence to Lena Claesson-Welsh, Department of Genetics and Pathology, Uppsala University, The Rudbeck Laboratory, Dag Hammarskjöldsv. 20, 751 85 Uppsala, Sweden. E-mail Lena.Welsh{at}genpat.uu.se
Objective— The purpose of this study was to clarify the role of fibroblast growth factors (FGFs) and FGF receptors (FGFRs) in hematopoietic/endothelial development.
Methods and Results— Using several different FGFR-1–specific antibodies and FGFR-1 promoter-driven LacZ activity, we show that FGFR-1 is expressed and active as a tyrosine kinase in a subpopulation of endothelial cells (
20% of the endothelial pool) during development in embryoid bodies. In agreement, in stem cell-derived teratomas, expression of FGFR-1 was detected in some but not all vessels. The FGFR-1 expressing endothelial cells were mitogenically active in the absence and presence of vascular endothelial growth factor (VEGF). Expression of FGFR-1 in endothelial cell precursors was not required for vascular development, and vascularization was enhanced in FGFR-1–deficient embryoid bodies compared with wild-type stem cells. In contrast, hematopoietic development was severely disturbed, with reduced expression of markers for primitive and definitive hematopoiesis.
Conclusions— Our data show that FGFR-1 is expressed in early hematopoietic/endothelial precursor cells, as well as in a subpool of endothelial cells in tumor vessels, and that it is critical for hematopoietic but not for vascular development.
Immunostaining using several different antibodies and scoring for FGFR-1 promoter-driven Lac Z activity show that some but not all endothelial cells express FGFR-1. FGFR-1 gene inactivation leads to a block in hematopoietic development; in contrast, endothelial cell development is enhanced.
Key Words: angiogenesis • endothelial cells • FGF receptor-1 • hematopoiesis • vasculogenesis
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