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L-Proline Induces a Mesenchymal-like Invasive Program in Embryonic Stem Cells by Remodeling H3K9 and H3K36 Methylation
Metabolites are emerging as key mediators of crosstalk between metabolic flux, cellular signaling, and epigenetic regulation of cell fate. We found that the nonessential amino acid L-proline (L-Pro) acts as a signaling molecule that promotes the conversion of embryonic stem cells into mesenchymal-li...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849245/ https://www.ncbi.nlm.nih.gov/pubmed/24319666 http://dx.doi.org/10.1016/j.stemcr.2013.09.001 |
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author | Comes, Stefania Gagliardi, Miriam Laprano, Nicola Fico, Annalisa Cimmino, Amelia Palamidessi, Andrea De Cesare, Dario De Falco, Sandro Angelini, Claudia Scita, Giorgio Patriarca, Eduardo J. Matarazzo, Maria R. Minchiotti, Gabriella |
author_facet | Comes, Stefania Gagliardi, Miriam Laprano, Nicola Fico, Annalisa Cimmino, Amelia Palamidessi, Andrea De Cesare, Dario De Falco, Sandro Angelini, Claudia Scita, Giorgio Patriarca, Eduardo J. Matarazzo, Maria R. Minchiotti, Gabriella |
author_sort | Comes, Stefania |
collection | PubMed |
description | Metabolites are emerging as key mediators of crosstalk between metabolic flux, cellular signaling, and epigenetic regulation of cell fate. We found that the nonessential amino acid L-proline (L-Pro) acts as a signaling molecule that promotes the conversion of embryonic stem cells into mesenchymal-like, spindle-shaped, highly motile, invasive pluripotent stem cells. This embryonic-stem-cell-to-mesenchymal-like transition (esMT) is accompanied by a genome-wide remodeling of the H3K9 and H3K36 methylation status. Consistently, L-Pro-induced esMT is fully reversible either after L-Pro withdrawal or by addition of ascorbic acid (vitamin C), which in turn reduces H3K9 and H3K36 methylation, promoting a mesenchymal-like-to-embryonic-stem-cell transition (MesT). These findings suggest that L-Pro, which is produced by proteolytic remodeling of the extracellular matrix, may act as a microenvironmental cue to control stem cell behavior. |
format | Online Article Text |
id | pubmed-3849245 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-38492452013-12-06 L-Proline Induces a Mesenchymal-like Invasive Program in Embryonic Stem Cells by Remodeling H3K9 and H3K36 Methylation Comes, Stefania Gagliardi, Miriam Laprano, Nicola Fico, Annalisa Cimmino, Amelia Palamidessi, Andrea De Cesare, Dario De Falco, Sandro Angelini, Claudia Scita, Giorgio Patriarca, Eduardo J. Matarazzo, Maria R. Minchiotti, Gabriella Stem Cell Reports Article Metabolites are emerging as key mediators of crosstalk between metabolic flux, cellular signaling, and epigenetic regulation of cell fate. We found that the nonessential amino acid L-proline (L-Pro) acts as a signaling molecule that promotes the conversion of embryonic stem cells into mesenchymal-like, spindle-shaped, highly motile, invasive pluripotent stem cells. This embryonic-stem-cell-to-mesenchymal-like transition (esMT) is accompanied by a genome-wide remodeling of the H3K9 and H3K36 methylation status. Consistently, L-Pro-induced esMT is fully reversible either after L-Pro withdrawal or by addition of ascorbic acid (vitamin C), which in turn reduces H3K9 and H3K36 methylation, promoting a mesenchymal-like-to-embryonic-stem-cell transition (MesT). These findings suggest that L-Pro, which is produced by proteolytic remodeling of the extracellular matrix, may act as a microenvironmental cue to control stem cell behavior. Elsevier 2013-10-10 /pmc/articles/PMC3849245/ /pubmed/24319666 http://dx.doi.org/10.1016/j.stemcr.2013.09.001 Text en © 2013 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Article Comes, Stefania Gagliardi, Miriam Laprano, Nicola Fico, Annalisa Cimmino, Amelia Palamidessi, Andrea De Cesare, Dario De Falco, Sandro Angelini, Claudia Scita, Giorgio Patriarca, Eduardo J. Matarazzo, Maria R. Minchiotti, Gabriella L-Proline Induces a Mesenchymal-like Invasive Program in Embryonic Stem Cells by Remodeling H3K9 and H3K36 Methylation |
title | L-Proline Induces a Mesenchymal-like Invasive Program in Embryonic Stem Cells by Remodeling H3K9 and H3K36 Methylation |
title_full | L-Proline Induces a Mesenchymal-like Invasive Program in Embryonic Stem Cells by Remodeling H3K9 and H3K36 Methylation |
title_fullStr | L-Proline Induces a Mesenchymal-like Invasive Program in Embryonic Stem Cells by Remodeling H3K9 and H3K36 Methylation |
title_full_unstemmed | L-Proline Induces a Mesenchymal-like Invasive Program in Embryonic Stem Cells by Remodeling H3K9 and H3K36 Methylation |
title_short | L-Proline Induces a Mesenchymal-like Invasive Program in Embryonic Stem Cells by Remodeling H3K9 and H3K36 Methylation |
title_sort | l-proline induces a mesenchymal-like invasive program in embryonic stem cells by remodeling h3k9 and h3k36 methylation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849245/ https://www.ncbi.nlm.nih.gov/pubmed/24319666 http://dx.doi.org/10.1016/j.stemcr.2013.09.001 |
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