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New Insights into the Mechanisms of Embryonic Stem Cell Self-Renewal under Hypoxia: A Multifactorial Analysis Approach

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  • Hélder S C Barbosa
  • Tiago G Fernandes
  • Tiago P Dias
  • Maria Margarida Diogo
  • Joaquim M S Cabral

Abstract

Previous reports have shown that culturing mouse embryonic stem (mES) cells at different oxygen tensions originated different cell proliferation patterns and commitment stages depending on which signaling pathways are activated or inhibited to support the pluripotency state. Herein we provide new insights into the mechanisms by which oxygen is influencing mES cell self-renewal and pluripotency. A multifactorial approach was developed to rationally evaluate the singular and interactive control of MEK/ERK pathway, GSK-3 inhibition, and LIF/STAT3 signaling at physiological and non-physiological oxygen tensions. Collectively, our methodology revealed a significant role of GSK-3-mediated signaling towards maintenance of mES cell pluripotency at lower O2 tensions. Given the central role of this signaling pathway, future studies will need to focus on the downstream mechanisms involved in ES cell self-renewal under such conditions, and ultimately how these findings impact human models of pluripotency.

Suggested Citation

  • Hélder S C Barbosa & Tiago G Fernandes & Tiago P Dias & Maria Margarida Diogo & Joaquim M S Cabral, 2012. "New Insights into the Mechanisms of Embryonic Stem Cell Self-Renewal under Hypoxia: A Multifactorial Analysis Approach," PLOS ONE, Public Library of Science, vol. 7(6), pages 1-13, June.
    • Handle: RePEc:plo:pone00:0038963
    DOI: 10.1371/journal.pone.0038963
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    References listed on IDEAS

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    1. Qi-Long Ying & Jason Wray & Jennifer Nichols & Laura Batlle-Morera & Bradley Doble & James Woodgett & Philip Cohen & Austin Smith, 2008. "The ground state of embryonic stem cell self-renewal," Nature, Nature, vol. 453(7194), pages 519-523, May.
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