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

Cristina D'Aniello, 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

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

36 Citaten (Scopus)

Samenvatting

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.

Originele taal-2Engels
Pagina's (van-tot)1-10
Aantal pagina's10
TijdschriftStem Cell Reports
Volume8
Nummer van het tijdschrift1
DOI's
StatusGepubliceerd - 10 jan. 2017
Extern gepubliceerdJa

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