Metabolic Effects on Mouse Embryonic Stem Cells and the Canonical Mammalian Target of Rapamycin Pathway

Diapause-like features can be extended to naïve mouse embryonic stem cells (mESCs) to induce paused pluripotency by using INK128 (mTi), a mammalian target of rapamycin (mTOR) inhibitor. As a core integrative pathway, mTOR senses diverse stimuli and translates these cues to coordinate several process...

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Main Authors: Bibiana Correia, Maria Inês Sousa, João Ramalho-Santos
Format: Article
Language:English
Published: MDPI AG 2023-11-01
Series:BioChem
Subjects:
Online Access:https://www.mdpi.com/2673-6411/3/4/12
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author Bibiana Correia
Maria Inês Sousa
João Ramalho-Santos
author_facet Bibiana Correia
Maria Inês Sousa
João Ramalho-Santos
author_sort Bibiana Correia
collection DOAJ
description Diapause-like features can be extended to naïve mouse embryonic stem cells (mESCs) to induce paused pluripotency by using INK128 (mTi), a mammalian target of rapamycin (mTOR) inhibitor. As a core integrative pathway, mTOR senses diverse stimuli and translates these cues to coordinate several processes. We have previously shown that the withdrawal of leucine and arginine from the culture medium of naïve mESCs can induce features of a paused-pluripotent state, including reduced cell proliferation, cell cycle arrest, and reductions in glycolytic and oxidative metabolism. However, surprisingly, although mTi did indeed provoke a paused-like state, this was distinct from and less pronounced than what resulted from leucine and arginine removal, and, according to our results, these features did not seem to necessarily be mTOR-driven. Therefore, this possibility should be considered in further experiments, and mTOR inhibition when using INK128 should always be confirmed and not merely assumed when INK128 is present in the culture medium.
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spelling doaj.art-c42b1be9d0334bddb6219e133a2b1fae2023-12-22T13:53:55ZengMDPI AGBioChem2673-64112023-11-013417018110.3390/biochem3040012Metabolic Effects on Mouse Embryonic Stem Cells and the Canonical Mammalian Target of Rapamycin PathwayBibiana Correia0Maria Inês Sousa1João Ramalho-Santos2Department of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, PortugalDepartment of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, PortugalDepartment of Life Sciences, University of Coimbra, Calçada Martim de Freitas, 3000-456 Coimbra, PortugalDiapause-like features can be extended to naïve mouse embryonic stem cells (mESCs) to induce paused pluripotency by using INK128 (mTi), a mammalian target of rapamycin (mTOR) inhibitor. As a core integrative pathway, mTOR senses diverse stimuli and translates these cues to coordinate several processes. We have previously shown that the withdrawal of leucine and arginine from the culture medium of naïve mESCs can induce features of a paused-pluripotent state, including reduced cell proliferation, cell cycle arrest, and reductions in glycolytic and oxidative metabolism. However, surprisingly, although mTi did indeed provoke a paused-like state, this was distinct from and less pronounced than what resulted from leucine and arginine removal, and, according to our results, these features did not seem to necessarily be mTOR-driven. Therefore, this possibility should be considered in further experiments, and mTOR inhibition when using INK128 should always be confirmed and not merely assumed when INK128 is present in the culture medium.https://www.mdpi.com/2673-6411/3/4/12leucineargininemTORmESCmetabolism
spellingShingle Bibiana Correia
Maria Inês Sousa
João Ramalho-Santos
Metabolic Effects on Mouse Embryonic Stem Cells and the Canonical Mammalian Target of Rapamycin Pathway
BioChem
leucine
arginine
mTOR
mESC
metabolism
title Metabolic Effects on Mouse Embryonic Stem Cells and the Canonical Mammalian Target of Rapamycin Pathway
title_full Metabolic Effects on Mouse Embryonic Stem Cells and the Canonical Mammalian Target of Rapamycin Pathway
title_fullStr Metabolic Effects on Mouse Embryonic Stem Cells and the Canonical Mammalian Target of Rapamycin Pathway
title_full_unstemmed Metabolic Effects on Mouse Embryonic Stem Cells and the Canonical Mammalian Target of Rapamycin Pathway
title_short Metabolic Effects on Mouse Embryonic Stem Cells and the Canonical Mammalian Target of Rapamycin Pathway
title_sort metabolic effects on mouse embryonic stem cells and the canonical mammalian target of rapamycin pathway
topic leucine
arginine
mTOR
mESC
metabolism
url https://www.mdpi.com/2673-6411/3/4/12
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AT mariainessousa metaboliceffectsonmouseembryonicstemcellsandthecanonicalmammaliantargetofrapamycinpathway
AT joaoramalhosantos metaboliceffectsonmouseembryonicstemcellsandthecanonicalmammaliantargetofrapamycinpathway