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Metabolic Profile Variations along the Differentiation of Human-Induced Pluripotent Stem Cells to Dopaminergic Neurons

In recent years, the availability of induced pluripotent stem cell-based neuronal models has opened new perspectives on the study and therapy of neurological diseases such as Parkinson’s disease. In particular, P. Zhang set up a protocol to efficiently generate dopaminergic neurons from induced plur...

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Autores principales: Carsana, Emma Veronica, Audano, Matteo, Breviario, Silvia, Pedretti, Silvia, Aureli, Massimo, Lunghi, Giulia, Mitro, Nico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495704/
https://www.ncbi.nlm.nih.gov/pubmed/36140170
http://dx.doi.org/10.3390/biomedicines10092069
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author Carsana, Emma Veronica
Audano, Matteo
Breviario, Silvia
Pedretti, Silvia
Aureli, Massimo
Lunghi, Giulia
Mitro, Nico
author_facet Carsana, Emma Veronica
Audano, Matteo
Breviario, Silvia
Pedretti, Silvia
Aureli, Massimo
Lunghi, Giulia
Mitro, Nico
author_sort Carsana, Emma Veronica
collection PubMed
description In recent years, the availability of induced pluripotent stem cell-based neuronal models has opened new perspectives on the study and therapy of neurological diseases such as Parkinson’s disease. In particular, P. Zhang set up a protocol to efficiently generate dopaminergic neurons from induced pluripotent stem cells. Although the differentiation process of these cells has been widely investigated, there is scant information related to the variation in metabolic features during the differentiation process of pluripotent stem cells to mature dopaminergic neurons. For this reason, we analysed the metabolic profile of induced pluripotent stem cells, neuronal precursors and mature neurons by liquid chromatography–tandem mass spectrometry. We found that induced pluripotent stem cells primarily rely on fatty acid beta-oxidation as a fuel source. Upon progression to neuronal progenitors, it was observed that cells began to shut down fatty acid β-oxidation and preferentially catabolised glucose, which is the principal source of energy in fully differentiated neurons. Interestingly, in neuronal precursors, we observed an increase in amino acids that are likely the result of increased uptake or synthesis, while in mature dopaminergic neurons, we also observed an augmented content of those amino acids needed for dopamine synthesis. In summary, our study highlights a metabolic rewiring occurring during the differentiation stages of dopaminergic neurons.
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spelling pubmed-94957042022-09-23 Metabolic Profile Variations along the Differentiation of Human-Induced Pluripotent Stem Cells to Dopaminergic Neurons Carsana, Emma Veronica Audano, Matteo Breviario, Silvia Pedretti, Silvia Aureli, Massimo Lunghi, Giulia Mitro, Nico Biomedicines Article In recent years, the availability of induced pluripotent stem cell-based neuronal models has opened new perspectives on the study and therapy of neurological diseases such as Parkinson’s disease. In particular, P. Zhang set up a protocol to efficiently generate dopaminergic neurons from induced pluripotent stem cells. Although the differentiation process of these cells has been widely investigated, there is scant information related to the variation in metabolic features during the differentiation process of pluripotent stem cells to mature dopaminergic neurons. For this reason, we analysed the metabolic profile of induced pluripotent stem cells, neuronal precursors and mature neurons by liquid chromatography–tandem mass spectrometry. We found that induced pluripotent stem cells primarily rely on fatty acid beta-oxidation as a fuel source. Upon progression to neuronal progenitors, it was observed that cells began to shut down fatty acid β-oxidation and preferentially catabolised glucose, which is the principal source of energy in fully differentiated neurons. Interestingly, in neuronal precursors, we observed an increase in amino acids that are likely the result of increased uptake or synthesis, while in mature dopaminergic neurons, we also observed an augmented content of those amino acids needed for dopamine synthesis. In summary, our study highlights a metabolic rewiring occurring during the differentiation stages of dopaminergic neurons. MDPI 2022-08-24 /pmc/articles/PMC9495704/ /pubmed/36140170 http://dx.doi.org/10.3390/biomedicines10092069 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Carsana, Emma Veronica
Audano, Matteo
Breviario, Silvia
Pedretti, Silvia
Aureli, Massimo
Lunghi, Giulia
Mitro, Nico
Metabolic Profile Variations along the Differentiation of Human-Induced Pluripotent Stem Cells to Dopaminergic Neurons
title Metabolic Profile Variations along the Differentiation of Human-Induced Pluripotent Stem Cells to Dopaminergic Neurons
title_full Metabolic Profile Variations along the Differentiation of Human-Induced Pluripotent Stem Cells to Dopaminergic Neurons
title_fullStr Metabolic Profile Variations along the Differentiation of Human-Induced Pluripotent Stem Cells to Dopaminergic Neurons
title_full_unstemmed Metabolic Profile Variations along the Differentiation of Human-Induced Pluripotent Stem Cells to Dopaminergic Neurons
title_short Metabolic Profile Variations along the Differentiation of Human-Induced Pluripotent Stem Cells to Dopaminergic Neurons
title_sort metabolic profile variations along the differentiation of human-induced pluripotent stem cells to dopaminergic neurons
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9495704/
https://www.ncbi.nlm.nih.gov/pubmed/36140170
http://dx.doi.org/10.3390/biomedicines10092069
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