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Prepatterning in the Stem Cell Compartment

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  • Peter D Tonge
  • Victor Olariu
  • Daniel Coca
  • Visakan Kadirkamanathan
  • Kelly E Burrell
  • Stephen A Billings
  • Peter W Andrews

Abstract

The mechanism by which an apparently uniform population of cells can generate a heterogeneous population of differentiated derivatives is a fundamental aspect of pluripotent and multipotent stem cell behaviour. One possibility is that the environment and the differentiation cues to which the cells are exposed are not uniform. An alternative, but not mutually exclusive possibility is that the observed heterogeneity arises from the stem cells themselves through the existence of different interconvertible substates that pre-exist before the cells commit to differentiate. We have tested this hypothesis in the case of apparently homogeneous pluripotent human embryonal carcinoma (EC) stem cells, which do not follow a uniform pattern of differentiation when exposed to retinoic acid. Instead, they produce differentiated progeny that include both neuronal and non-neural phenotypes. Our results suggest that pluripotent NTERA2 stem cells oscillate between functionally distinct substates that are primed to select distinct lineages when differentiation is induced.

Suggested Citation

  • Peter D Tonge & Victor Olariu & Daniel Coca & Visakan Kadirkamanathan & Kelly E Burrell & Stephen A Billings & Peter W Andrews, 2010. "Prepatterning in the Stem Cell Compartment," PLOS ONE, Public Library of Science, vol. 5(5), pages 1-10, May.
    • Handle: RePEc:plo:pone00:0010901
    DOI: 10.1371/journal.pone.0010901
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    References listed on IDEAS

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    1. Ian Chambers & Jose Silva & Douglas Colby & Jennifer Nichols & Bianca Nijmeijer & Morag Robertson & Jan Vrana & Ken Jones & Lars Grotewold & Austin Smith, 2007. "Nanog safeguards pluripotency and mediates germline development," Nature, Nature, vol. 450(7173), pages 1230-1234, December.
    2. Hamparsum Bozdogan, 1987. "Model selection and Akaike's Information Criterion (AIC): The general theory and its analytical extensions," Psychometrika, Springer;The Psychometric Society, vol. 52(3), pages 345-370, September.
    3. Hannah H. Chang & Martin Hemberg & Mauricio Barahona & Donald E. Ingber & Sui Huang, 2008. "Transcriptome-wide noise controls lineage choice in mammalian progenitor cells," Nature, Nature, vol. 453(7194), pages 544-547, May.
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