Please use this identifier to cite or link to this item: https://doi.org/10.1002/jcp.22214
Title: FGF-2 modulates Wnt signaling in undifferentiated hESC and iPS cells through activated PI3-K/GSK3β signaling
Authors: Ding, V.M.Y.
Ling, L.
Natarajan, S.
Yap, M.G.S.
Cool, S.M.
CHOO BOON HWA,ANDRE 
Issue Date: Nov-2010
Citation: Ding, V.M.Y., Ling, L., Natarajan, S., Yap, M.G.S., Cool, S.M., CHOO BOON HWA,ANDRE (2010-11). FGF-2 modulates Wnt signaling in undifferentiated hESC and iPS cells through activated PI3-K/GSK3β signaling. Journal of Cellular Physiology 225 (2) : 417-428. ScholarBank@NUS Repository. https://doi.org/10.1002/jcp.22214
Abstract: Fibroblast growth factor-2 (FGF-2) is widely used to culture human embryonic stem cells (hESC) and induced pluripotent stem (iPS) cells. Despite its importance in maintaining undifferentiated hESC phenotype, a lack of understanding in the role of FGF-2 still exists. Here, we investigate the signaling events in hESC following the addition of exogenous FGF-2. In this study, we show that hESC express all forms of fibroblast growth factor receptors (FGFRs) which co-localize on Oct3/4 positive cells. Furthermore, downregulation of Oct3/4 in hESC occurs following treatment with an FGFR inhibitor, suggesting that FGF signaling may regulate Oct3/4 expression. This is also observed in iPS cells. Also, downstream of FGF signaling, both mitogen activated protein kinase (MAPK) and phosphoinositide 3-kinase pathways (PI3-K) are activated following FGF-2 stimulation. Notably, inhibition of MAPK and PI3-K signaling using specific kinase inhibitors revealed that activated PI3-K, rather than MAPK, can mediate pluripotent marker expression. To understand the importance of PI3-K activation, activation of Wnt/β-catenin by FGF-2 was investigated. Wnt signaling had been implicated to have a role in maintaining of pluripotent hESC. We found that upon FGF-2 stimulation, GSK3β is phosphorylated following which nuclear translocation of β-catenin and TCF/LEF activation occurs. Interestingly, inhibition of the Wnt pathway with Dikkopf-1 (DKK-1) resulted in only partial suppression of the FGF-2 induced TCF/LEF activity. Prolonged culture of hESC with DKK-1 did not affect pluripotent marker expression. These results suggest that FGF-2 mediated PI3-K signaling may have a direct role in modulating the downstream of Wnt pathway to maintain undifferentiated hESC. © 2010 Wiley-Liss, Inc.
Source Title: Journal of Cellular Physiology
URI: http://scholarbank.nus.edu.sg/handle/10635/67057
ISSN: 00219541
DOI: 10.1002/jcp.22214
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

67
checked on Sep 20, 2018

WEB OF SCIENCETM
Citations

66
checked on Sep 10, 2018

Page view(s)

43
checked on Aug 3, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.