title: Modulation of the pentose phosphate pathway induces endodermal differentiation in embryonic stem cells.
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.
authors.affiliation: Stem Cell Fate Lab, Institute of Genetics and Biophysics "A. Buzzati Traverso" CNR, Naples, Italy.
authors.forename: Genesia
authors.initials: G
authors.lastname: Manganelli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Fico
authors.forename: Ugo
authors.initials: U
authors.lastname: Masullo
authors.forename: Fabiana
authors.initials: F
authors.lastname: Pizzolongo
authors.forename: Amelia
authors.initials: A
authors.lastname: Cimmino
authors.forename: Stefania
authors.initials: S
authors.lastname: Filosa
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000201:enzymology; D004707:Endoderm / Q000166:cytology*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D051379:Mice; D010427:Pentose Phosphate Pathway
chemical_list: D005954:Glucosephosphate Dehydrogenase