TY - JOUR
T1 - Vitamin C and L-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum
AU - D'Aniello, Cristina
AU - Habibi, Ehsan
AU - Cermola, Federica
AU - Paris, Debora
AU - Russo, Francesco
AU - Fiorenzano, Alessandro
AU - Di Napoli, Gabriele
AU - Melck, Dominique J.
AU - Cobellis, Gilda
AU - Angelini, Claudia
AU - Fico, Annalisa
AU - Blelloch, Robert
AU - Motta, Andrea
AU - Stunnenberg, Hendrik G.
AU - De Cesare, Dario
AU - Patriarca, Eduardo J.
AU - Minchiotti, Gabriella
N1 - Publisher Copyright:
© 2017 The Authors
PY - 2017/1/10
Y1 - 2017/1/10
N2 - 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.
AB - 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.
KW - DNA methylation
KW - early primed pluripotency
KW - L-proline
KW - metabolic reprogramming
KW - metabolomics
KW - naive pluripotency
KW - vitamin C
UR - http://www.scopus.com/inward/record.url?scp=85009084580&partnerID=8YFLogxK
U2 - 10.1016/j.stemcr.2016.11.011
DO - 10.1016/j.stemcr.2016.11.011
M3 - Article
C2 - 28017658
AN - SCOPUS:85009084580
SN - 2213-6711
VL - 8
SP - 1
EP - 10
JO - Stem Cell Reports
JF - Stem Cell Reports
IS - 1
ER -