SIGNALING PATHWAYS REGULATING PROLIFERATION OF MURINE EMBRYONIC STEM CELLS
I. A. Chuykin,1 M. S. Lianguzova, V. A. Pospelov
Institute of Cytology RAN, St. Petersburg;
1 e-mail: chuykin79@mail.ru
Murine embryonic stem cells (mESC) are capable of unlimiting proliferation with maintenance of pluripotency
during long-term cultivation. Signaling pathways regulating the cell cycle of mESC are of the great interest
for further investigation. This review concerns to the cell cycle regulation of mESC through different signaling
pathways (LIF-STAT3, PI3K-Akt, Wnt-β-catenin) and to the mechanisms of unlimited proliferation of
mESC and their inability to undergo long-term block of proliferation in response to DNA-damaging and stress
factors. The functioning of negative cell cycle regulators (cyclin-kinase inhibitors and Rb) and positive cell cycle
regulators (cyclin-kinase complexes and E2F factors) are also topics of this review. It is considered that, permanent
mitogenic stimuli are needed to prevent induction of apoptosis. Therefore, the agents which cause prolonged
halt of proliferation without ongoing onset of differentiation or induction of apoptosis are currently unknown.
The main focus is given to the role of the Wnt signaling pathway in sustaining the pluripotent state of
mESC. The cell cycle regulation by downstream targets of LIF-STAT3, PI3-kinase and Wnt-β-catenin pathways
is discussed in light of cooperative action of these pathways for maintenance of undifferentiated state of
mESC.
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