Expression and potential role of fibroblast growth factor 2 and its receptors in human embryonic stem cells

. 2005 Sep ; 23 (8) : 1200-11. [epub] 20050613

Jazyk angličtina Země Anglie, Velká Británie Médium print-electronic

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/pmid15955829

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.

Citace poskytuje Crossref.org

Nejnovějších 20 citací...

Zobrazit více v
Medvik | PubMed

Aminophylline Induces Two Types of Arrhythmic Events in Human Pluripotent Stem Cell-Derived Cardiomyocytes

. 2021 ; 12 () : 789730. [epub] 20220117

DMD Pluripotent Stem Cell Derived Cardiac Cells Recapitulate in vitro Human Cardiac Pathophysiology

. 2020 ; 8 () : 535. [epub] 20200619

NANOG/NANOGP8 Localizes at the Centrosome and is Spatiotemporally Associated with Centriole Maturation

. 2020 Mar 11 ; 9 (3) : . [epub] 20200311

Both Hypoxia-Inducible Factor 1 and MAPK Signaling Pathway Attenuate PI3K/AKT via Suppression of Reactive Oxygen Species in Human Pluripotent Stem Cells

. 2020 ; 8 () : 607444. [epub] 20210121

Dystrophin Deficiency Leads to Genomic Instability in Human Pluripotent Stem Cells via NO Synthase-Induced Oxidative Stress

. 2019 Jan 15 ; 8 (1) : . [epub] 20190115

Regulation of ciliary function by fibroblast growth factor signaling identifies FGFR3-related disorders achondroplasia and thanatophoric dysplasia as ciliopathies

. 2018 Mar 15 ; 27 (6) : 1093-1105.

One reporter for in-cell activity profiling of majority of protein kinase oncogenes

. 2017 Feb 15 ; 6 () : . [epub] 20170215

The Aberrant DNA Methylation Profile of Human Induced Pluripotent Stem Cells Is Connected to the Reprogramming Process and Is Normalized During In Vitro Culture

. 2016 ; 11 (6) : e0157974. [epub] 20160623

Forced aggregation and defined factors allow highly uniform-sized embryoid bodies and functional cardiomyocytes from human embryonic and induced pluripotent stem cells

. 2014 Nov ; 29 (6) : 834-46. [epub] 20131121

Mutation frequency dynamics in HPRT locus in culture-adapted human embryonic stem cells and induced pluripotent stem cells correspond to their differentiated counterparts

. 2014 Oct 15 ; 23 (20) : 2443-54. [epub] 20140725

Cultivation-dependent plasticity of melanoma phenotype

. 2013 Dec ; 34 (6) : 3345-55. [epub] 20130612

Nonlinear regression models for determination of nicotinamide adenine dinucleotide content in human embryonic stem cells

. 2013 Dec ; 9 (6) : 786-93.

A complex role for FGF-2 in self-renewal, survival, and adhesion of human embryonic stem cells

. 2009 Aug ; 27 (8) : 1847-57.

Najít záznam

Citační ukazatele

Nahrávání dat ...

Možnosti archivace

Nahrávání dat ...