Work previously performed in our group showed that culturing mouse embryonic stem (mES) cells under different oxygen tensions gave rise to different cell proliferation patterns and commitment stages dependent on which signaling pathways are activated/inhibited to support mES cell self-renewal. However, a clear understanding of the molecular mechanisms that regulate stem cell fate and function under these conditions is mostly lacking. To systematically investigate these effects, the sole and interactive influence of MEK/ERK pathway inhibition, activation of Wnt/�-Catenin and activation of STAT3 signaling, were statistically evaluated during expansion of mES cells at different oxygen tensions using a factorial design. This modeling approach revealed that at lower O2 tensions STAT3 signaling and Wnt/�-Catenin are indispensable for cell self-renewal and pluripotency. Our results add new insights into the mechanisms by which oxygen tension influences mES cell fate, and GSK-3� inhibition, in particular, showed an important role towards maintenance of ES cell pluripotency.

Multifactorial analysis of embryonic stem cell self-renewal reveals a crucial role of GSK-3β-mediated signaling at physiological oxygen levels

243rd National Meeting (2012)

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