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

doi:10.1016/j.stemcr.2016.11.011

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

Research output: Contribution to journal › Article › peer-review

37 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1-10
Number of pages	10
Journal	Stem Cell Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1016/j.stemcr.2016.11.011
Publication status	Published - 10 Jan 2017
Externally published	Yes

Keywords

DNA methylation
early primed pluripotency
L-proline
metabolic reprogramming
metabolomics
naive pluripotency
vitamin C

Access to Document

10.1016/j.stemcr.2016.11.011

Cite this

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. (2017). Vitamin C and L-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum. Stem Cell Reports, 8(1), 1-10. https://doi.org/10.1016/j.stemcr.2016.11.011

@article{5f67219e850f4a63953fb40bc745ff34,

title = "Vitamin C and L-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum",

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.",

keywords = "DNA methylation, early primed pluripotency, L-proline, metabolic reprogramming, metabolomics, naive pluripotency, vitamin C",

author = "Cristina D'Aniello and Ehsan Habibi and Federica Cermola and Debora Paris and Francesco Russo and Alessandro Fiorenzano and {Di Napoli}, Gabriele and Melck, {Dominique J.} and Gilda Cobellis and Claudia Angelini and Annalisa Fico and Robert Blelloch and Andrea Motta and Stunnenberg, {Hendrik G.} and {De Cesare}, Dario and Patriarca, {Eduardo J.} and Gabriella Minchiotti",

note = "Publisher Copyright: {\textcopyright} 2017 The Authors",

year = "2017",

month = jan,

day = "10",

doi = "10.1016/j.stemcr.2016.11.011",

language = "English",

volume = "8",

pages = "1--10",

journal = "Stem Cell Reports",

issn = "2213-6711",

publisher = "Cell Press",

number = "1",

}

D'Aniello, C, Habibi, E, Cermola, F, Paris, D, Russo, F, Fiorenzano, A, Di Napoli, G, Melck, DJ, Cobellis, G, Angelini, C, Fico, A, Blelloch, R, Motta, A, Stunnenberg, HG, De Cesare, D, Patriarca, EJ & Minchiotti, G 2017, 'Vitamin C and L-Proline Antagonistic Effects Capture Alternative States in the Pluripotency Continuum', Stem Cell Reports, vol. 8, no. 1, pp. 1-10. https://doi.org/10.1016/j.stemcr.2016.11.011

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

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 -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this