Modulation of the pentose phosphate pathway induces endodermal differentiation in embryonic stem cells

Genesia Manganelli, Annalisa Fico, Ugo Masullo, Fabiana Pizzolongo, Amelia Cimmino, Stefania Filosa

Research output: Contribution to journalArticle

Abstract

Embryonic stem (ES) cells can differentiate in vitro into a variety of cell types. Efforts to produce endodermal cell derivatives, including lung, liver and pancreas, have been met with modest success. Understanding how the endoderm originates from ES cells is the first step to generate specific cell types for therapeutic purposes. Recently, it has been demonstrated that inhibition of Myc or mTOR induces endodermal differentiation. Both Myc and mTOR are known to be activators of the Pentose Phosphate Pathway (PPP). We found that, differentely from wild type (wt), ES cells unable to produce pentose sugars through PPP differentiate into endodermal precursors in cell culture conditions generally non-permissive to generate them. The same effect was observed when wt ES cells were differentiated in presence of chemical inhibitors of the PPP. These data highlight a new role for metabolism. Indeed, to our knowledge, it is the first time that modulation of a metabolic pathway is described to be crucial in determining ES cell fate.

Original languageEnglish
Article numbere29321
JournalPLoS One
Volume7
Issue number1
DOIs
Publication statusPublished - Jan 12 2012

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Manganelli, G., Fico, A., Masullo, U., Pizzolongo, F., Cimmino, A., & Filosa, S. (2012). Modulation of the pentose phosphate pathway induces endodermal differentiation in embryonic stem cells. PLoS One, 7(1), [e29321]. https://doi.org/10.1371/journal.pone.0029321