Generation of a primitive erythroid cell line and promotion of its growth by basic fibroblast growth factor.
An immortalized cell line representing the primitive erythroid (EryP) lineage was established from in vitro-differentiated progeny (embryoid bodies [EBs]) of embryonic stem (ES) cells using a retroviral insertional mutation, and has been termed EB-PE for embryoid body-derived primitive erythroid. Even though EB-PE cells are immortalized, they show characteristics of normal EryP cells, such as gene expression and growth factor dependency. In addition, EB-PE cells can differentiate further in culture. Investigation of growth factor requirements of EB-PE cells showed that basic fibroblast growth factor (bFGF) and erythropoietin (Epo) play unique roles in EB-PE proliferation and differentiation. While bFGF was a strong mitogen, Epo was required for both proliferation and differentiation. The unique proliferative response to bFGF coincided with upregulation of its receptor, fibroblast growth factor receptor (fgfr-1), and downregulation of erythropoietin receptor (EpoR) gene expression. Studies of primary EryP cells derived from early EBs, when tested in a colony-formation assay, also provided evidence for the mitogenic role of bFGF in concert with Epo.
Yuen
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Department of Pathology, Molecular and Cell Biology Program, University of Maryland at Baltimore, Baltimore, MD, USA.
Mittal
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L
Deng
C X
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Choi
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K
D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D004622:Embryo, Mammalian / Q000166:cytology; D016228:Endothelial Growth Factors / Q000494:pharmacology; D015672:Erythroid Precursor Cells / Q000502:physiology*; D004921:Erythropoietin / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D015870:Gene Expression; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D008222:Lymphokines / Q000494:pharmacology; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D017467:Receptors, Erythropoietin / Q000502:physiology; D017468:Receptors, Fibroblast Growth Factor / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics; D013234:Stem Cells / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D012333:RNA, Messenger; D017467:Receptors, Erythropoietin; D017468:Receptors, Fibroblast Growth Factor; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D004921:Erythropoietin; D007334:Insulin-Like Growth Factor I; C496349:Fgfr1 protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1