| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Original Article |
1 Department of Molecular Embryology, Institute of Experimental Medicine AS CR
2 Department of Internal Medicine - Hematooncology, University Hospital Brno
3 Center for Cell Therapy and Tissue Repair, Charles University
4 Laboratory of Molecular Embryology, Mendel University Brno
* To whom correspondence should be addressed. E-mail: dvorakp{at}mendelu.cz.
 |
Abstract |
|---|
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 characterised expression of FGF-2, the prototypic member of the FGF family, and its receptors (FGFRs) in undifferentiated and differentiating hESCs; and subsequently we analyzed the effects of FGF-2 on hESCs, acting as both exogenous and endogenous factor.
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 order: FGFR1 > FGFR3 > FGFR4 > FGFR2. Initiation of differentiation is accompanied by profound changes in FGFR expression, particularly the up-regulation 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 hESCs colonies with time in culture. Finally, the inhibitor of FGFRs, SU5402, was used to ascertain whether or not 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 and/or differentiation of hESCs.
This article has been cited by other articles:
|
|
 |
|
  M. K. Furue, J. Na, J. P. Jackson, T. Okamoto, M. Jones, D. Baker, R.-I. Hata, H. D. Moore, J. D. Sato, and P. W. Andrews Heparin promotes the growth of human embryonic stem cells in a defined serum-free medium PNAS, September 9, 2008; 105(36): 13409 - 13414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Yu and J. A. Thomson Pluripotent stem cell lines Genes & Dev., August 1, 2008; 22(15): 1987 - 1997. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Mayshar, E. Rom, I. Chumakov, A. Kronman, A. Yayon, and N. Benvenisty Fibroblast Growth Factor 4 and Its Novel Splice Isoform Have Opposing Effects on the Maintenance of Human Embryonic Stem Cell Self-Renewal Stem Cells, March 1, 2008; 26(3): 767 - 774. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Go, C. Takenaka, and H. Ohgushi Effect of Forced Expression of Basic Fibroblast Growth Factor in Human Bone Marrow-Derived Mesenchymal Stromal Cells J. Biochem., December 1, 2007; 142(6): 741 - 748. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wang, T. C. Schulz, E. S. Sherrer, D. S. Dauphin, S. Shin, A. M. Nelson, C. B. Ware, M. Zhan, C.-Z. Song, X. Chen, et al. Self-renewal of human embryonic stem cells requires insulin-like growth factor-1 receptor and ERBB2 receptor signaling Blood, December 1, 2007; 110(12): 4111 - 4119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Greber, H. Lehrach, and J. Adjaye Fibroblast Growth Factor 2 Modulates Transforming Growth Factor {beta} Signaling in Mouse Embryonic Fibroblasts and Human ESCs (hESCs) to Support hESC Self-Renewal Stem Cells, February 1, 2007; 25(2): 455 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Babaie, R. Herwig, B. Greber, T. C. Brink, W. Wruck, D. Groth, H. Lehrach, T. Burdon, and J. Adjaye Analysis of Oct4-Dependent Transcriptional Networks Regulating Self-Renewal and Pluripotency in Human Embryonic Stem Cells Stem Cells, February 1, 2007; 25(2): 500 - 510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Timmer, K. Cesnulevicius, C. Winkler, J. Kolb, E. Lipokatic-Takacs, J. Jungnickel, and C. Grothe Fibroblast Growth Factor (FGF)-2 and FGF Receptor 3 Are Required for the Development of the Substantia Nigra, and FGF-2 Plays a Crucial Role for the Rescue of Dopaminergic Neurons after 6-Hydroxydopamine Lesion J. Neurosci., January 17, 2007; 27(3): 459 - 471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-E. Zaragosi, G. Ailhaud, and C. Dani Autocrine Fibroblast Growth Factor 2 Signaling Is Critical for Self-Renewal of Human Multipotent Adipose-Derived Stem Cells Stem Cells, November 1, 2006; 24(11): 2412 - 2419. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Armstrong, O. Hughes, S. Yung, L. Hyslop, R. Stewart, I. Wappler, H. Peters, T. Walter, P. Stojkovic, J. Evans, et al. The role of PI3K/AKT, MAPK/ERK and NF{kappa}{beta} signalling in the maintenance of human embryonic stem cell pluripotency and viability highlighted by transcriptional profiling and functional analysis Hum. Mol. Genet., June 1, 2006; 15(11): 1894 - 1913. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Koellensperger, D. von Heimburg, M. Markowicz, and N. Pallua Human Serum from Platelet-Poor Plasma for the Culture of Primary Human Preadipocytes Stem Cells, May 1, 2006; 24(5): 1218 - 1225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yu, M. A. Vodyanik, P. He, I. I. Slukvin, and J. A. Thomson Human Embryonic Stem Cells Reprogram Myeloid Precursors Following Cell-Cell Fusion Stem Cells, January 1, 2006; 24(1): 168 - 176. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| STEM CELLS | THE ONCOLOGIST | CME | ALPHAMED PRESS JOURNALS |
