L-Proline Induces a Mesenchymal-like Invasive Program in Embryonic Stem Cells by Remodeling H3K9 and H3K36 Methylation

被引：80
作者：
Comes, Stefania [1 ,2 ]
Gagliardi, Miriam [2 ]
Laprano, Nicola [1 ,2 ]
Fico, Annalisa [1 ,2 ]
Cimmino, Amelia [1 ,2 ]
Palamidessi, Andrea [3 ]
De Cesare, Dario [1 ,2 ]
De Falco, Sandro [1 ,2 ]
Angelini, Claudia [4 ]
Scita, Giorgio [3 ,5 ]
Patriarca, Eduardo J. [1 ,2 ]
Matarazzo, Maria R. [2 ]
Minchiotti, Gabriella [1 ,2 ]
机构：
[1] CNR, Inst Genet & Biophys A Buzzati Traverso, Stem Cell Fate Lab, I-80131 Naples, Italy
[2] CNR, Inst Genet & Biophys A Buzzati Traverso, I-80131 Naples, Italy
[3] IFOM, IEO, Inst Mol Oncol Fdn, FIRC, I-20139 Milan, Italy
[4] CNR, Inst Appl Math Mauro Picone, I-80131 Naples, Italy
[5] Univ Milan, Dipartimento Sci Salute, I-20142 Milan, Italy
来源：
STEM CELL REPORTS | 2013年 / 1卷 / 04期
基金：
欧洲研究理事会;
关键词：
SELF-RENEWAL; PROGENITOR CELLS; ES CELLS; METABOLISM; DIFFERENTIATION; EPIGENETICS; CATABOLISM; CANCER; METASTASIS; DERIVATION;
D O I：
10.1016/j.stemcr.2013.09.001
中图分类号：
Q813 [细胞工程];
学科分类号：
摘要：
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.
引用
收藏
页码：307 / 321
页数：15
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