FDC-P1 myeloid cells engineered to express fibroblast growth factor receptor 1 proliferate and differentiate in the presence of fibroblast growth factor and heparin.
Full-length murine fibroblast growth factor (FGF) receptor 1 (FGFR-1L) cDNA was introduced into the FDC-P1 mouse myeloid progenitor cell line, which lacks FGF receptors and depends on interleukin 3 (IL-3) or granulocyte/macrophage colony-stimulating factor (GM-CSF) for its proliferation and survival. The expression of the FGFR-1L gene in FDC-P1 cells allowed these cells to grow in the presence of FGF and heparin. The resulting cell line, designated FD FGFR-1L.A, exhibited a more mature myeloid phenotype than did the parental FD FGFR-1L cells or uninfected FDC-P1 cells. They formed mainly dispersed colonies in soft-agar cultures when grown in the presence of FGF and heparin, suggestive of myeloid differentiation. The cells can be switched between growth on FGF/heparin and IL-3. Northern blot analysis and cytochemical staining demonstrated that FD FGFR-1L.A cells expressed myeloperoxidase mRNA and protein, biochemical markers specifically expressed during differentiation from the promyelocytic to the granulocytic stages, whereas the parental FD FGFR-1L cells and FDC-P1 cells failed to express this marker. These results indicate that the expression of FGFR-1L by FDC-P1 cells transmitted signals for growth in the presence of FGF and heparin and generated an additional signal for early myeloid differentiation but failed to commit FD FGFR-1L.A cells to terminal differentiation. This in vitro culture system can be used for molecular analysis of the regulation of cellular growth and differentiation mediated by the FGFs and their receptors.
Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.
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D000818:Animals; D015152:Blotting, Northern; D002417:Cattle; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006133:Growth Substances / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D009195:Peroxidase / Q000235:genetics / Q000378:metabolism; D011061:Poly A / Q000235:genetics / Q000302:isolation & purification; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins / Q000494:pharmacology; D014162:Transfection
D006133:Growth Substances; D007377:Interleukin-3; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D011061:Poly A; D012313:RNA; D006493:Heparin; D009195:Peroxidase