In vitro generation of long-term repopulating hematopoietic stem cells by fibroblast growth factor-1.
The role of fibroblast growth factors and their receptors (FGFRs) in the regulation of normal hematopoietic stem cells is unknown. Here we show that, in mouse bone marrow, long-term repopulating stem cells are found exclusively in the FGFR(+) cell fraction. During differentiation toward committed progenitors, stem cells show loss of FGFR expression. Prolonged culture of bone marrow cells in serum-free medium supplemented with only FGF-1 resulted in robust expansion of multilineage, serially transplantable, long-term repopulating hematopoietic stem cells. Thus, we have identified a simple method of generating large numbers of rapidly engrafting stem cells that have not been genetically manipulated. Our results show that the multipotential properties of stem cells are dependent on signaling through FGF receptors and that FGF-1 plays an important role in hematopoietic stem cell homeostasis.
de Haan
Gerald
G
Department of Stem Cell Biology, University of Groningen, A Deusinglaan 1, 9713 AV Groningen, The Netherlands. g.de.haan@med.rug.nl
Weersing
Ellen
E
Dontje
Bert
B
van Os
Ronald
R
Bystrykh
Leonid V
LV
Vellenga
Edo
E
Miller
Geraldine
G
D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation; D019070:Cell Lineage; D017931:DNA Primers / Q000737:chemistry; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D006410:Hematopoiesis / Q000502:physiology; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014916:Whole-Body Irradiation
D018952:Antigens, CD34; D017931:DNA Primers; D007141:Immunoglobulin Fc Fragments; D017468:Receptors, Fibroblast Growth Factor; D016220:Fibroblast Growth Factor 1