Vitamin C and L-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2016 Dec 27

PMID 28017658

Citations 27

Authors

Cristina DAniello

Ehsan Habibi

Federica Cermola

Debora Paris

Francesco Russo

Alessandro Fiorenzano

Gabriele Di Napoli

Dominique J Melck

Gilda Cobellis

Claudia Angelini

Annalisa Fico

Robert Blelloch

Andrea Motta

Hendrik G Stunnenberg

Dario De Cesare

Eduardo J Patriarca

Gabriella Minchiotti

Affiliations

Soon will be listed here.

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.

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