Pluripotent Stem Cell Metabolism and Mitochondria: Beyond ATP

Metabolism is central to embryonic stem cell (ESC) pluripotency and differentiation, with distinct profiles apparent under different nutrient milieu, and conditions that maintain alternate cell states. The significance of altered nutrient availability, particularly oxygen, and metabolic pathway acti...

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Main Authors: Jarmon G. Lees, David K. Gardner, Alexandra J. Harvey
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2017/2874283
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author Jarmon G. Lees
David K. Gardner
Alexandra J. Harvey
author_facet Jarmon G. Lees
David K. Gardner
Alexandra J. Harvey
author_sort Jarmon G. Lees
collection DOAJ
description Metabolism is central to embryonic stem cell (ESC) pluripotency and differentiation, with distinct profiles apparent under different nutrient milieu, and conditions that maintain alternate cell states. The significance of altered nutrient availability, particularly oxygen, and metabolic pathway activity has been highlighted by extensive studies of their impact on preimplantation embryo development, physiology, and viability. ESC similarly modulate their metabolism in response to altered metabolite levels, with changes in nutrient availability shown to have a lasting impact on derived cell identity through the regulation of the epigenetic landscape. Further, the preferential use of glucose and anaplerotic glutamine metabolism serves to not only support cell growth and proliferation but also minimise reactive oxygen species production. However, the perinuclear localisation of spherical, electron-poor mitochondria in ESC is proposed to sustain ESC nuclear-mitochondrial crosstalk and a mitochondrial-H2O2 presence, to facilitate signalling to support self-renewal through the stabilisation of HIFα, a process that may be favoured under physiological oxygen. The environment in which a cell is grown is therefore a critical regulator and determinant of cell fate, with metabolism, and particularly mitochondria, acting as an interface between the environment and the epigenome.
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spelling doaj-art-0e812618dc394fffac4192d7d3df70bf2025-02-03T06:05:34ZengWileyStem Cells International1687-966X1687-96782017-01-01201710.1155/2017/28742832874283Pluripotent Stem Cell Metabolism and Mitochondria: Beyond ATPJarmon G. Lees0David K. Gardner1Alexandra J. Harvey2School of BioSciences, University of Melbourne, Parkville, VIC 3010, AustraliaSchool of BioSciences, University of Melbourne, Parkville, VIC 3010, AustraliaSchool of BioSciences, University of Melbourne, Parkville, VIC 3010, AustraliaMetabolism is central to embryonic stem cell (ESC) pluripotency and differentiation, with distinct profiles apparent under different nutrient milieu, and conditions that maintain alternate cell states. The significance of altered nutrient availability, particularly oxygen, and metabolic pathway activity has been highlighted by extensive studies of their impact on preimplantation embryo development, physiology, and viability. ESC similarly modulate their metabolism in response to altered metabolite levels, with changes in nutrient availability shown to have a lasting impact on derived cell identity through the regulation of the epigenetic landscape. Further, the preferential use of glucose and anaplerotic glutamine metabolism serves to not only support cell growth and proliferation but also minimise reactive oxygen species production. However, the perinuclear localisation of spherical, electron-poor mitochondria in ESC is proposed to sustain ESC nuclear-mitochondrial crosstalk and a mitochondrial-H2O2 presence, to facilitate signalling to support self-renewal through the stabilisation of HIFα, a process that may be favoured under physiological oxygen. The environment in which a cell is grown is therefore a critical regulator and determinant of cell fate, with metabolism, and particularly mitochondria, acting as an interface between the environment and the epigenome.http://dx.doi.org/10.1155/2017/2874283
spellingShingle Jarmon G. Lees
David K. Gardner
Alexandra J. Harvey
Pluripotent Stem Cell Metabolism and Mitochondria: Beyond ATP
Stem Cells International
title Pluripotent Stem Cell Metabolism and Mitochondria: Beyond ATP
title_full Pluripotent Stem Cell Metabolism and Mitochondria: Beyond ATP
title_fullStr Pluripotent Stem Cell Metabolism and Mitochondria: Beyond ATP
title_full_unstemmed Pluripotent Stem Cell Metabolism and Mitochondria: Beyond ATP
title_short Pluripotent Stem Cell Metabolism and Mitochondria: Beyond ATP
title_sort pluripotent stem cell metabolism and mitochondria beyond atp
url http://dx.doi.org/10.1155/2017/2874283
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