Modulation of the pentose phosphate pathway induces endodermal differentiation in embryonic stem cells.
Modulation of the pentose phosphate pathway induces endodermal differentiation in embryonic stem cells.
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DOI：
10.1371/journal.pone.0029321
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Filosa S
中科院分区：
文献类型：
--
作者：
Manganelli G;Fico A;Masullo U;Pizzolongo F;Cimmino A;Filosa S
胚胎干细胞（ES细胞）可以在体外分化为多种细胞类型。努力生产内胚层细胞衍生物，包括肺，肝和胰腺，已经取得了一定的成功。了解内胚层如何起源于ES细胞是产生用于治疗目的的特定细胞类型的第一步。最近，已经证明抑制Myc或mTOR诱导内胚层分化。已知Myc和mTOR都是戊糖磷酸途径（PPP）的激活剂。我们发现，与野生型（wt）不同，不能通过PPP产生戊糖的ES细胞在通常不允许产生它们的细胞培养条件下分化成内胚层前体。当在PPP的化学抑制剂的存在下分化wt ES细胞时，观察到相同的效果。这些数据突出了新陈代谢的新作用。事实上，据我们所知，这是第一次描述代谢途径的调节在决定ES细胞命运中至关重要。
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.
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