Expression and potential role of fibroblast growth factor 2 and its receptors in human embryonic stem cells
Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
15955829
DOI
10.1634/stemcells.2004-0303
PII: 2004-0303
Knihovny.cz E-zdroje
- MeSH
- buněčná diferenciace MeSH
- embryo savčí cytologie MeSH
- fibroblastový růstový faktor 2 biosyntéza fyziologie MeSH
- fosforylace MeSH
- kmenové buňky cytologie účinky léků metabolismus MeSH
- lidé MeSH
- mitogenem aktivované proteinkinasy metabolismus MeSH
- protein - isoformy MeSH
- pyrroly farmakologie MeSH
- receptor fibroblastových růstových faktorů, typ 2 biosyntéza fyziologie MeSH
- receptory fibroblastových růstových faktorů biosyntéza fyziologie MeSH
- signální transdukce fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- FGFR2 protein, human MeSH Prohlížeč
- fibroblastový růstový faktor 2 MeSH
- mitogenem aktivované proteinkinasy MeSH
- protein - isoformy MeSH
- pyrroly MeSH
- receptor fibroblastových růstových faktorů, typ 2 MeSH
- receptory fibroblastových růstových faktorů MeSH
- SU 5402 MeSH Prohlížeč
Although the detection of several components of the fibroblast growth factor (FGF) signaling pathway in human embryonic stem cells (hESCs) has been reported, the functionality of that pathway and effects on cell fate decisions are yet to be established. In this study we characterized expression of FGF-2, the prototypic member of the FGF family, and its receptors (FGFRs) in undifferentiated and differentiating hESCs; subsequently, we analyzed the effects of FGF-2 on hESCs, acting as both exogenous and endogenous factors. We have determined that undifferentiated hESCs are abundant in several molecular-mass isoforms of FGF-2 and that expression pattern of these isoforms remains unchanged under conditions that induce hESC differentiation. Significantly, FGF-2 is released by hESCs into the medium, suggesting an autocrine activity. Expression of FGFRs in undifferentiated hESCs follows a specific pattern, with FGFR1 being the most abundant species and other receptors showing lower expression in the following order: FGFR1 --> FGFR3 --> FGFR4 --> FGFR2. Initiation of differentiation is accompanied by profound changes in FGFR expression, particularly the upregulation of FGFR1. When hESCs are exposed to exogenous FGF-2, extracellular signal-regulated kinases are phosphorylated and thereby activated. However, the presence or absence of exogenous FGF-2 does not significantly affect the proliferation of hESCs. Instead, increased concentration of exogenous FGF-2 leads to reduced outgrowth of hESC colonies with time in culture. Finally, the inhibitor of FGFRs, SU5402, was used to ascertain whether FGF-2 that is released by hESCs exerts its activities via autocrine pathways. Strikingly, the resultant inhibition of FGFR suppresses activation of downstream protein kinases and causes rapid cell differentiation, suggesting an involvement of autocrine FGF signals in the maintenance of proliferating hESCs in the undifferentiated state. In conclusion from our data, we propose that this endogenous FGF signaling pathway can be implicated in self-renewal or differentiation of hESCs.
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