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Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell Model

Given the considerable interest in using stem cells for modeling and treating disease, it is essential to understand what regulates self-renewal and differentiation. Remodeling of mitochondria and metabolism, with the shift from glycolysis to oxidative phosphorylation (OXPHOS), plays a fundamental r...

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Autores principales: Mostafavi, Sepideh, Balafkan, Novin, Pettersen, Ina Katrine Nitschke, Nido, Gonzalo S., Siller, Richard, Tzoulis, Charalampos, Sullivan, Gareth J., Bindoff, Laurence A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553110/
https://www.ncbi.nlm.nih.gov/pubmed/34722525
http://dx.doi.org/10.3389/fcell.2021.744777
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author Mostafavi, Sepideh
Balafkan, Novin
Pettersen, Ina Katrine Nitschke
Nido, Gonzalo S.
Siller, Richard
Tzoulis, Charalampos
Sullivan, Gareth J.
Bindoff, Laurence A.
author_facet Mostafavi, Sepideh
Balafkan, Novin
Pettersen, Ina Katrine Nitschke
Nido, Gonzalo S.
Siller, Richard
Tzoulis, Charalampos
Sullivan, Gareth J.
Bindoff, Laurence A.
author_sort Mostafavi, Sepideh
collection PubMed
description Given the considerable interest in using stem cells for modeling and treating disease, it is essential to understand what regulates self-renewal and differentiation. Remodeling of mitochondria and metabolism, with the shift from glycolysis to oxidative phosphorylation (OXPHOS), plays a fundamental role in maintaining pluripotency and stem cell fate. It has been suggested that the metabolic “switch” from glycolysis to OXPHOS is germ layer-specific as glycolysis remains active during early ectoderm commitment but is downregulated during the transition to mesoderm and endoderm lineages. How mitochondria adapt during these metabolic changes and whether mitochondria remodeling is tissue specific remain unclear. Here, we address the question of mitochondrial adaptation by examining the differentiation of human pluripotent stem cells to cardiac progenitors and further to differentiated mesodermal derivatives, including functional cardiomyocytes. In contrast to recent findings in neuronal differentiation, we found that mitochondrial content decreases continuously during mesoderm differentiation, despite increased mitochondrial activity and higher levels of ATP-linked respiration. Thus, our work highlights similarities in mitochondrial remodeling during the transition from pluripotent to multipotent state in ectodermal and mesodermal lineages, while at the same time demonstrating cell-lineage-specific adaptations upon further differentiation. Our results improve the understanding of how mitochondrial remodeling and the metabolism interact during mesoderm differentiation and show that it is erroneous to assume that increased OXPHOS activity during differentiation requires a simultaneous expansion of mitochondrial content.
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spelling pubmed-85531102021-10-29 Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell Model Mostafavi, Sepideh Balafkan, Novin Pettersen, Ina Katrine Nitschke Nido, Gonzalo S. Siller, Richard Tzoulis, Charalampos Sullivan, Gareth J. Bindoff, Laurence A. Front Cell Dev Biol Cell and Developmental Biology Given the considerable interest in using stem cells for modeling and treating disease, it is essential to understand what regulates self-renewal and differentiation. Remodeling of mitochondria and metabolism, with the shift from glycolysis to oxidative phosphorylation (OXPHOS), plays a fundamental role in maintaining pluripotency and stem cell fate. It has been suggested that the metabolic “switch” from glycolysis to OXPHOS is germ layer-specific as glycolysis remains active during early ectoderm commitment but is downregulated during the transition to mesoderm and endoderm lineages. How mitochondria adapt during these metabolic changes and whether mitochondria remodeling is tissue specific remain unclear. Here, we address the question of mitochondrial adaptation by examining the differentiation of human pluripotent stem cells to cardiac progenitors and further to differentiated mesodermal derivatives, including functional cardiomyocytes. In contrast to recent findings in neuronal differentiation, we found that mitochondrial content decreases continuously during mesoderm differentiation, despite increased mitochondrial activity and higher levels of ATP-linked respiration. Thus, our work highlights similarities in mitochondrial remodeling during the transition from pluripotent to multipotent state in ectodermal and mesodermal lineages, while at the same time demonstrating cell-lineage-specific adaptations upon further differentiation. Our results improve the understanding of how mitochondrial remodeling and the metabolism interact during mesoderm differentiation and show that it is erroneous to assume that increased OXPHOS activity during differentiation requires a simultaneous expansion of mitochondrial content. Frontiers Media S.A. 2021-10-14 /pmc/articles/PMC8553110/ /pubmed/34722525 http://dx.doi.org/10.3389/fcell.2021.744777 Text en Copyright © 2021 Mostafavi, Balafkan, Pettersen, Nido, Siller, Tzoulis, Sullivan and Bindoff. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cell and Developmental Biology
Mostafavi, Sepideh
Balafkan, Novin
Pettersen, Ina Katrine Nitschke
Nido, Gonzalo S.
Siller, Richard
Tzoulis, Charalampos
Sullivan, Gareth J.
Bindoff, Laurence A.
Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell Model
title Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell Model
title_full Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell Model
title_fullStr Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell Model
title_full_unstemmed Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell Model
title_short Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell Model
title_sort distinct mitochondrial remodeling during mesoderm differentiation in a human-based stem cell model
topic Cell and Developmental Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553110/
https://www.ncbi.nlm.nih.gov/pubmed/34722525
http://dx.doi.org/10.3389/fcell.2021.744777
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