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Abstract
Pluripotent mouse embryonic stem (ES) cells can be expanded in large numbers in vitro
owing to a process of symmetrical self-renewal. Self-renewal entails proliferation
with a concomitant suppression of differentiation. Here we describe how the cytokine
leukaemia inhibitory factor (LIF) sustains self-renewal through activation of the
transcription factor STAT3, and how two other signals - extracellular-signal-related
kinase (ERK) and phosphatidylinositol-3-OH kinase (PI3K) - can influence differentiation
and propagation, respectively. We relate these observations to the unusual cell-cycle
properties of ES cells and speculate on the role of the cell cycle in maintaining
pluripotency.