Metabolites and cofactors are emerging as key regulators of cell plasticity and reprogramming, and their role in the control of pluripotency is just being discovered. Here we provide unprecedented evidence that embryonic stem cell (ESC) pluripotency relies on the relative levels of two physiological metabolites, namely ascorbic acid (vitamin C, VitC) and L-proline (L-Pro), which affect global DNA methylation, transcriptional profile, and energy metabolism. Specifically, while a high VitC/L-Pro ratio drives ESCs toward a naive state, the opposite condition (L-Pro excess) captures a fully reversible early primed pluripotent state, which depends on autocrine fibroblast growth factor and transforming growth factor β signaling pathways. Our findings highlight the pivotal role of metabolites availability in controlling the pluripotency continuum from naive to primed states.
Vitamin C and L-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum / D'Aniello, C.; Habibi, E.; Cermola, F.; Paris, D.; Russo, F.; Fiorenzano, A.; Di Napoli, G.; Melck, D. J.; Cobellis, G.; Angelini, C.; Fico, A.; Blelloch, R.; Motta, A.; Stunnenberg, H. G.; De Cesare, D.; Patriarca, E. J.; Minchiotti, G.. - In: STEM CELL REPORTS. - ISSN 2213-6711. - 8:1(2017), pp. 1-10. [10.1016/j.stemcr.2016.11.011]
Vitamin C and L-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum
Fiorenzano A.;Melck D. J.;
2017
Abstract
Metabolites and cofactors are emerging as key regulators of cell plasticity and reprogramming, and their role in the control of pluripotency is just being discovered. Here we provide unprecedented evidence that embryonic stem cell (ESC) pluripotency relies on the relative levels of two physiological metabolites, namely ascorbic acid (vitamin C, VitC) and L-proline (L-Pro), which affect global DNA methylation, transcriptional profile, and energy metabolism. Specifically, while a high VitC/L-Pro ratio drives ESCs toward a naive state, the opposite condition (L-Pro excess) captures a fully reversible early primed pluripotent state, which depends on autocrine fibroblast growth factor and transforming growth factor β signaling pathways. Our findings highlight the pivotal role of metabolites availability in controlling the pluripotency continuum from naive to primed states.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
