http://www.cnr.it/ontology/cnr/individuo/prodotto/ID27049

Control of embryonic stem cell metastability by L-proline catabolism. (Articolo in rivista)

Type

Label

Control of embryonic stem cell metastability by L-proline catabolism. (Articolo in rivista) (literal)

Anno

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Alternative label

Casalino L, Comes S, Lambazzi G, De Stefano B, Filosa S, De Falco S, De Cesare D, Minchiotti G, Patriarca EJ. (2011)
Control of embryonic stem cell metastability by L-proline catabolism.
in Journal of Molecular Cell Biology (Print); Oxford University Press, Oxford (Regno Unito)
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Casalino L, Comes S, Lambazzi G, De Stefano B, Filosa S, De Falco S, De Cesare D, Minchiotti G, Patriarca EJ. (literal)

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Note

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CNR, Stem Cell Fate Lab, Inst Genet & Biophys A Buzzati Traverso, I-80125 Naples, Italy (literal)

Titolo

Abstract

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. (literal)

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