RETRACTED: Contribution of the PI3K/Akt/PKB signal pathway to maintenance of self‐renewal in human embryonic stem cells

Abstract

Although basic fibroblast growth factor (FGF2) is generally included in the media for maintenance of human embryonic stem cells (hESCs), the action of FGF2 in these cells has not been well defined. Here, we determined the roles of FGF2 in maintaining hESC self-renewal. Withdrawal of FGF2 from the media led to acquisition of typical differentiated characteristics in hESCs. In the presence of FGF2, which is normally required for proliferation in an undifferentiated state, inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt/PKB signal stimulated differentiation and attenuated the expression of extracellular matrix (ECM) molecules. We suggest that FGF2 maintains hESC self-renewal by supporting stable expression of ECM molecules through activation of the PI3K/Akt/PKB pathway.

Activation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells

“…Our results cast a new light on Akt signaling, namely, Akt signaling regulates the pluripotency as well as the proliferation of ES cells. Recently, inhibition of PI3K/Akt signaling in mouse and human ES cells was reported to induce differentiation of the ES cell in the presence of LIF and feeder cells, respectively (Paling et al, 2004;Kim et al, 2005), which supports the claim for the importance of Akt signaling in ES cell differentiation.…”

“…In human ES cells, basic FGF sustains undifferentiated proliferation in collaboration with Noggin, the inhibitor of BMP signaling (Xu et al, 2005). In addition, the treatment with blocking antibodies against a 6 b 1 integrin induces the differentiation of human ES cells (Kim et al, 2005). Thus, multiple signaling would cooperatively regulate the ES cell pluripotency through the activation of PI3K/Akt signaling.…”

Toward xeno-free culture of human embryonic stem cells

“…It has recently been proposed that FGF acts as a competence factor for activin/Nodal/TGFβ in the maintenance of pluripotency/self-renewal and that the Wnt signaling cascade feeds into this pathway (Vallier et al, 2005). This role for FGF may involve activation of the PI-3-kinase/Akt pathway (Kim et al, 2005) although direct evidence for this has to be established. Finally, inhibition of the BMP signaling pathway, which is suggested to drive differentiation of hESCs, may also be important (Xu, Peck, et al, 2005).…”

Efficient culture system for human embryonic stem cells using autologous human embryonic stem cell-derived feeder cells

“…However, this method does require media conditioned by MEFs cultured with fetal bovine serum (FBS). Moreover, the stable and long-term culture of hESCs and the maintenance of their undifferentiated state still requires feeder cells along with the addition of exogenous basic fibroblast growth factor (bFGF) (Kim et al, 2005c).…”