Control of embryonic stem cell metastability by L-proline catabolism
| العنوان: | Control of embryonic stem cell metastability by L-proline catabolism |
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| المؤلفون: | Stefania Comes, Eduardo J. Patriarca, Dario De Cesare, Benedetta De Stefano, Gabriella Minchiotti, Giuseppina Lambazzi, Stefania Filosa, Laura Casalino, Sandro De Falco |
| المصدر: | Advances in Stem Cell Research: Stem Cells in developement, Regeneration and Disease, Parigi, 2011 info:cnr-pdr/source/autori:Casalino Laura, Comes Stefania, Lambazzi Giuseppina, De Stefano Benedetta, Filosa Stefania, De Falco Sandro, De Cesare Dario, Minchiotti Gabriella, and Patriarca Eduardo Jorge/congresso_nome:Advances in Stem Cell Research: Stem Cells in developement, Regeneration and Disease/congresso_luogo:Parigi/congresso_data:2011/anno:2011/pagina_da:/pagina_a:/intervallo_pagine Journal of Molecular Cell Biology 3 (2011): 108–122. doi:10.1093/jmcb/mjr001 info:cnr-pdr/source/autori:Casalino L, Comes S, Lambazzi G, De Stefano B, Filosa S, De Falco S, De Cesare D, Minchiotti G, Patriarca EJ./titolo:Control of embryonic stem cell metastability by L-proline catabolism./doi:10.1093%2Fjmcb%2Fmjr001/rivista:Journal of Molecular Cell Biology (Print)/anno:2011/pagina_da:108/pagina_a:122/intervallo_pagine:108–122/volume:3 |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, Pluripotent Stem Cells, Proline, Cell, Mice, SCID, Cell Line, Mice, Fibroblast growth factor-5, Genetics, medicine, Animals, Humans, Molecular Biology, reproductive and urinary physiology, Cells, Cultured, Embryonic Stem Cells, Cell Proliferation, biology, Catabolism, urogenital system, Embryo, Cell Differentiation, Cell Biology, General Medicine, Phenotype, Embryonic stem cell, embryonic stem cells, L-proline, vitamin C, colony phenotype, pluripotent states, metastability, medicine.anatomical_structure, Biochemistry, Epiblast, embryonic structures, Female, biology.gene, Stem cell |
| الوصف: | The molecular mechanisms controlling mouse embryonic stem cell (ESC) metastability, i.e. their capacity to fluctuate between different states of pluripotency, are not fully resolved. We developed and used a novel automation platform, the Cell(maker), to screen a library of metabolites on two ESC-based phenotypic assays (i.e. proliferation and colony phenotype) and identified two metabolically related amino acids, namely L-proline (L-Pro) and L-ornithine (L-Orn), as key regulators of ESC metastability. Both compounds, but mainly L-Pro, force ESCs toward a novel epiblast stem cell (EpiSC)-like state, in a dose-and time-dependent manner. Unlike EpiSCs, L-Pro-induced cells (PiCs) contribute to chimeric embryos and rely on leukemia inhibitor factor (LIF) to self-renew. Furthermore, PiCs revert to ESCs or differentiate randomly upon removal of either L-Pro or LIF, respectively. Remarkably, PiC generation depends on both L-Pro metabolism (uptake and oxidation) and Fgf5 induction, and is strongly counteracted by antioxidants, mainly L-ascorbic acid (vitamin C, Vc). ESCs PiCs phenotypic transition thus represents a previously undefined dynamic equilibrium between pluripotent states, which can be unbalanced either toward an EpiSC-like or an ESC phenotype by L-Pro/L-Orn or Vc treatments, respectively. All together, our data provide evidence that ESC metastability can be regulated at a metabolic level. |
| تدمد: | 1759-4685 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::46cca979da3f3aec01b5471d09b0ef85Test https://pubmed.ncbi.nlm.nih.gov/21307025Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....46cca979da3f3aec01b5471d09b0ef85 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17594685 |
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