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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.744777/full |
| _version_ | 1818577308919791616 |
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| author | Sepideh Mostafavi Novin Balafkan Novin Balafkan Novin Balafkan Ina Katrine Nitschke Pettersen Gonzalo S. Nido Gonzalo S. Nido Richard Siller Charalampos Tzoulis Charalampos Tzoulis Gareth J. Sullivan Gareth J. Sullivan Gareth J. Sullivan Gareth J. Sullivan Gareth J. Sullivan Gareth J. Sullivan Laurence A. Bindoff Laurence A. Bindoff |
| author_facet | Sepideh Mostafavi Novin Balafkan Novin Balafkan Novin Balafkan Ina Katrine Nitschke Pettersen Gonzalo S. Nido Gonzalo S. Nido Richard Siller Charalampos Tzoulis Charalampos Tzoulis Gareth J. Sullivan Gareth J. Sullivan Gareth J. Sullivan Gareth J. Sullivan Gareth J. Sullivan Gareth J. Sullivan Laurence A. Bindoff Laurence A. Bindoff |
| author_sort | Sepideh Mostafavi |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-16T06:27:51Z |
| format | Article |
| id | doaj.art-e22044775e98443d8c641f0853982412 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-16T06:27:51Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-e22044775e98443d8c641f08539824122022-12-21T22:40:57ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-10-01910.3389/fcell.2021.744777744777Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell ModelSepideh Mostafavi0Novin Balafkan1Novin Balafkan2Novin Balafkan3Ina Katrine Nitschke Pettersen4Gonzalo S. Nido5Gonzalo S. Nido6Richard Siller7Charalampos Tzoulis8Charalampos Tzoulis9Gareth J. Sullivan10Gareth J. Sullivan11Gareth J. Sullivan12Gareth J. Sullivan13Gareth J. Sullivan14Gareth J. Sullivan15Laurence A. Bindoff16Laurence A. Bindoff17Department of Clinical Medicine, University of Bergen, Bergen, NorwayDepartment of Clinical Medicine, University of Bergen, Bergen, NorwayDivision of Psychiatry, Haukeland University Hospital, Bergen, NorwayNorwegian Centre for Mental Disorders Research (NORMENT)—Centre of Excellence, Haukeland University Hospital, Bergen, NorwayInstitute for Biomedicine, University of Bergen, Bergen, NorwayDepartment of Clinical Medicine, University of Bergen, Bergen, NorwayNeuro-SysMed, Center of Excellence for Clinical Research in Neurological Diseases, Department of Neurology, Haukeland University Hospital, Bergen, NorwayStem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, University of Oslo, Oslo, NorwayDepartment of Clinical Medicine, University of Bergen, Bergen, NorwayNeuro-SysMed, Center of Excellence for Clinical Research in Neurological Diseases, Department of Neurology, Haukeland University Hospital, Bergen, NorwayStem Cell Epigenetics Laboratory, Institute of Basic Medical Sciences, University of Oslo, Oslo, NorwayDepartment of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, NorwayNorwegian Center for Stem Cell Research, Oslo University Hospital and the University of Oslo, Oslo, NorwayInstitute of Immunology, Oslo University Hospital, Oslo, Norway0Hybrid Technology Hub—Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway1Department of Pediatric Research, Oslo University Hospital, Oslo, NorwayDepartment of Clinical Medicine, University of Bergen, Bergen, NorwayNeuro-SysMed, Center of Excellence for Clinical Research in Neurological Diseases, Department of Neurology, Haukeland University Hospital, Bergen, NorwayGiven 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.https://www.frontiersin.org/articles/10.3389/fcell.2021.744777/fullmitochondriadevelopmentmetabolismstem cellscardiomyocyteOXPHOS |
| spellingShingle | Sepideh Mostafavi Novin Balafkan Novin Balafkan Novin Balafkan Ina Katrine Nitschke Pettersen Gonzalo S. Nido Gonzalo S. Nido Richard Siller Charalampos Tzoulis Charalampos Tzoulis Gareth J. Sullivan Gareth J. Sullivan Gareth J. Sullivan Gareth J. Sullivan Gareth J. Sullivan Gareth J. Sullivan Laurence A. Bindoff Laurence A. Bindoff Distinct Mitochondrial Remodeling During Mesoderm Differentiation in a Human-Based Stem Cell Model Frontiers in Cell and Developmental Biology mitochondria development metabolism stem cells cardiomyocyte OXPHOS |
| 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 | mitochondria development metabolism stem cells cardiomyocyte OXPHOS |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.744777/full |
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