Aged iPSCs display an uncommon mitochondrial appearance and fail to undergo in vitro neurogenesis

Masotti, Andrea; Celluzzi, Antonella; Petrini, Stefania; Bertini, Enrico; Zanni, Ginevra; Compagnucci, Claudia

doi:10.18632/aging.100708

Cited by 26 publications

(34 citation statements)

References 55 publications

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“…These data emphasize that different levels of mitochondrial maturation and metabolism predilection exist, depending on the pluripotency stage. In the same vein, iPSCs maintained for extended in vitro culture periods display increased mitochondrial content and reduced potential to undergo neurogenesis in comparison with young iPSCs [25]. These data emphasize the importance of controlling the precise pluripotency stage and time in culture of stem cells in studies interested in their pluripotency and metabolic features.…”

Section: Opposite Mitochondrial Remodeling and Metabolic Shifts Durinmentioning

confidence: 71%

Connecting Mitochondria, Metabolism, and Stem Cell Fate

Wanet

Arnould

Najimi

et al. 2015

Stem Cells and Development

260

216

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As sites of cellular respiration and energy production, mitochondria play a central role in cell metabolism. Cell differentiation is associated with an increase in mitochondrial content and activity and with a metabolic shift toward increased oxidative phosphorylation activity. The opposite occurs during reprogramming of somatic cells into induced pluripotent stem cells. Studies have provided evidence of mitochondrial and metabolic changes during the differentiation of both embryonic and somatic (or adult) stem cells (SSCs), such as hematopoietic stem cells, mesenchymal stem cells, and tissue-specific progenitor cells. We thus propose to consider those mitochondrial and metabolic changes as hallmarks of differentiation processes. We review how mitochondrial biogenesis, dynamics, and function are directly involved in embryonic and SSC differentiation and how metabolic and sensing pathways connect mitochondria and metabolism with cell fate and pluripotency. Understanding the basis of the crosstalk between mitochondria and cell fate is of critical importance, given the promising application of stem cells in regenerative medicine. In addition to the development of novel strategies to improve the in vitro lineage-directed differentiation of stem cells, understanding the molecular basis of this interplay could lead to the identification of novel targets to improve the treatment of degenerative diseases.

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Section: Opposite Mitochondrial Remodeling and Metabolic Shifts Durinmentioning

confidence: 71%

Connecting Mitochondria, Metabolism, and Stem Cell Fate

Wanet

Arnould

Najimi

et al. 2015

Stem Cells and Development

260

216

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“…As adult neural stem cells differentiate in vitro to neurons they also decrease aerobic glycolysis though a HIF1α-independent mechanism [25]. Interestingly pre-neural cells that retain an elevated number of mitochondria have a neuronal stem cell differentiation defect [29], emphasizing the developmental link between metabolic flux and cell fate decisions.…”

Section: Introductionmentioning

confidence: 99%

Metabolic switching and cell fate decisions: implications for pluripotency, reprogramming and development

Cliff

Dalton

2017

Current Opinion in Genetics & Development

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Cell fate decisions are closely linked to changes in metabolic activity. Over recent years this connection has been implicated in mechanisms underpinning embryonic development, reprogramming and disease pathogenesis. In addition to being important for supporting the energy demands of different cell types, metabolic switching from aerobic glycolysis to oxidative phosphorylation plays a critical role in controlling biosynthetic processes, intracellular redox state, epigenetic status and reactive oxygen species levels. These processes extend beyond ATP synthesis by impacting cell proliferation, differentiation, enzymatic activity, ageing and genomic integrity. This review will focus on how metabolic switching impacts decisions made by multipotent cells and discusses mechanisms by which this occurs.

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“…[27][28][29][30][31] Hence, comprehensive testing of iPSCs and their potential aging signature should be conducted. In the current study, we sought to thoroughly investigate the aging characteristics of iPSCs derived from aged somatic cells.…”

Section: Discussionmentioning

confidence: 99%

Rejuvenation of Cardiac Tissue Developed from Reprogrammed Aged Somatic Cells

Cheng

Peng

Zhang

et al. 2017

Rejuvenation Research

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Induced pluripotent stem cells (iPSCs) derived via somatic cell reprogramming have been reported to reset aged somatic cells to a more youthful state, characterized by elongated telomeres, a rearranged mitochondrial network, reduced oxidative stress, and restored pluripotency. However, it is still unclear whether the reprogrammed aged somatic cells can function normally as embryonic stem cells (ESCs) during development and be rejuvenated. In the current study, we applied the aggregation technique to investigate whether iPSCs derived from aged somatic cells could develop normally and be rejuvenated. iPSCs derived from bone marrow myeloid cells of 2-month-old (2 M) and 18-month-old (18 M) C57BL/6-Tg (CAG-EGFP)1Osb/J mice were aggregated with embryos derived from wild-type ICR mice to produce chimeras (referred to as 2 M CA and 18 M CA, respectively). Our observations focused on comparing the ability of the iPSCs derived from 18 M and 2 M bone marrow cells to develop rejuvenated cardiac tissue (the heart is the most vital organ during aging). The results showed an absence of p16 and p53 upregulation, telomere length shortening, and mitochondrial gene expression and deletion in 18 M CA, whereas slight changes in mitochondrial ultrastructure, cytochrome C oxidase activity, ATP production, and reactive oxygen species production were observed in CA cardiac tissues. The data implied that all of the aging characteristics observed in the newborn cardiac tissue of 18 M CA were comparable with those of 2 M CA newborn cardiac tissue. This study provides the first direct evidence of the aging-related characteristics of cardiac tissue developed from aged iPSCs, and our observations demonstrate that partial rejuvenation can be achieved by reprogramming aged somatic cells to a pluripotent state.

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Aged iPSCs display an uncommon mitochondrial appearance and fail to undergo in vitro neurogenesis

Cited by 26 publications

References 55 publications

Connecting Mitochondria, Metabolism, and Stem Cell Fate

Connecting Mitochondria, Metabolism, and Stem Cell Fate

Metabolic switching and cell fate decisions: implications for pluripotency, reprogramming and development

Rejuvenation of Cardiac Tissue Developed from Reprogrammed Aged Somatic Cells

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