Above the landscape
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Science Translational Medicine 25 Nov 2015:
Vol. 7, Issue 315, pp. 315ec205
Pluripotent stem cells can self-renew and differentiate into all cell types of the body, giving rise to all adult tissues starting with the embryo. Two stages of pluripotent states in both mouse and human embryonic stem (ES) cells have been reported: naïve (pre-implantation) and primed (post-implantation). Naïve ES cells show higher developmental potential than primed ES cells. In addition, these stages have distinct epigenetic profiles. In a new study, Sperber et al. reveal that not only the epigenetic signatures, but also the metabolic signatures are unique in both pluripotent states, with the primed state being highly glycolytic compared with naïve.
The naïve-to-primed transition showed a reduction in Wnt signaling, electron transport chain activity, and fatty acid β-oxidation, as well as activation of pathways involved in lipid biosynthesis and HIF-1α stabilization. In addition to glycolysis and fatty acid metabolism, amino acid metabolism differed between naïve and primed ES cells. Moreover, the authors revealed that the availability of S-adenosyl methionine triggers a cascade of epigenetic modifications, which suggests that the metabolome regulates the epigenetic landscape during human development. Despite the fact that the epigenetic profiles are very different between naïve and primed ES cells, little is known about the molecular mechanism causing these differences. Nevertheless, the authors’ findings suggest the possibility of changing the epigenome by manipulating metabolites.
H. Sperber et al., The metabolome regulates the epigenetic landscape during naïve-to-primed human embryonic stem cell transition. Nat. Cell Biol. 10.1038/ncb3264 (2015). [Abstract]
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