S16-05 Conserved function of STAT3 in mouse and rat embryonic stem cell self-renewal

STAT3 belongs to the signal transducers and activators of transcription (STAT) family. Activation of STAT3 via the LIF receptor/ gp130 signaling complex allows the derivation and propagation of embryonic stem (ES) cells from mouse blastocysts in the presence of feeders. Intriguingly, ES cells have not been established from some strains of mice, and not at all from rats under the LIF/feeder condition. We hypothesized that the STAT3 activation level is critical for regulating ES cell self-renewal. We introduced an STAT3 transgene and an artificial gp130 chimeric receptor into feeder-dependent mouse ES cells. This allows us to modulate STAT3 activity within a wider range in ES cells. We demonstrated that feeder-dependent mouse ES cells can be maintained in feeder-free conditions simply by modulating STAT3 activation level. We also showed that long-term self-renewal of rat ES cells can be sustained by increasing STAT3 activation, whereas LIF alone can not. These data suggest that the STAT3 activation level plays a key role in sustaining ES cell self-renewal and its function may be conserved among different strains of mice and rats.