Research Topic

Influence of Mitochondrial DNA in iPSCs Reprogramming

About this Research Topic

Induced pluripotent stem cells (iPSCs), which are pluripotent stem cells generated from somatic cells, hold promise in the field of regenerative medicine. iPSCs propagate indefinitely, can be induced to form various cell types in the body, and represent a single source of cells used to replace those lost to damage or disease. iPSCs must be safe to be used for transplantation purposes in regenerative medicine; accordingly, a great deal of effort has been devoted to ascertaining iPSC safety. To date, however, mitochondrial (mt) DNA has not been adequately considered.

mtDNA mutations accumulate during aging and cause “heteroplasmy,” a state in which normal and mutant type mtDNA molecules co-exist within a cell. When the proportion of mtDNA mutations exceeds a threshold, excessive heteroplasmy levels cause mitochondrial dysfunction. mtDNA mutations can arise and become enriched during reprogramming to generate iPSCs. Therefore, iPSC-derived products should be screened for mtDNA mutations.

Over half a century ago, Warburg initiated research on mitochondrial alterations in cancer and proposed a mechanism to explain the differences in energy metabolism between normal and cancer cells. The accumulated evidence indicates that heteroplasmy attributed to mtDNA mutations is linked to neurodegenerative diseases, aging, and cancer.

Currently, no convenient method exists to reduce the proportion of mutant mtDNA, which would be crucial for the treatment of heteroplasmy-attributed disorders and future stem-cell therapies. It has recently been discovered a novel and universal mechanism responsible for mtDNA inheritance, including restoration of homoplasmy from heteroplasmy, through recombination-driven mtDNA rolling-circle replication, which can be activated by an optimal level of reactive oxygen species (ROS) in human cells. ROS-stimulated mt-allele segregation via rolling-circle mtDNA replication may provide either mtDNA mutation-rich iPSCs, iPSCs with a lower proportion of mutant mtDNA in heteroplasmy, or iPSCs with wild-type mtDNA homoplasmy. iPSCs with high levels of mtDNA mutations may be a suitable source of cells for human mitochondrial disease modeling, and iPSCs with lower proportions of mutant mtDNA would ensure the safety of iPSCs upon differentiation into somatic cells for autologous transplantation. Endogenous ROS that act in mitochondrial signaling should not be regarded as risk factors for cellular metabolism.

We welcome Original Research, Methods, Reviews, Hypothesis and Theory, Perspectives and other article types.

The scope of this Research Topic may focus on the following specific themes:
1. The mechanisms for mtDNA replication, repair, and segregation during reprogramming, or in iPSCs.
2. Mitochondrial quality control such as mtDNA turnover processes by mitophagy, especially during iPSCs reprogramming
3. Roles of ROS from during reprogramming of iPSCs.
4. Roles of mitochondrial function during differentiation of iPSCs, and/or during reprogramming to generate iPSCs.
5. Analysis of mechanisms of action of chemical compounds using iPSCs.
6. mtDNA mutation-attributed disease modeling in iPSCs, or other stem cells.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

Induced pluripotent stem cells (iPSCs), which are pluripotent stem cells generated from somatic cells, hold promise in the field of regenerative medicine. iPSCs propagate indefinitely, can be induced to form various cell types in the body, and represent a single source of cells used to replace those lost to damage or disease. iPSCs must be safe to be used for transplantation purposes in regenerative medicine; accordingly, a great deal of effort has been devoted to ascertaining iPSC safety. To date, however, mitochondrial (mt) DNA has not been adequately considered.

mtDNA mutations accumulate during aging and cause “heteroplasmy,” a state in which normal and mutant type mtDNA molecules co-exist within a cell. When the proportion of mtDNA mutations exceeds a threshold, excessive heteroplasmy levels cause mitochondrial dysfunction. mtDNA mutations can arise and become enriched during reprogramming to generate iPSCs. Therefore, iPSC-derived products should be screened for mtDNA mutations.

Over half a century ago, Warburg initiated research on mitochondrial alterations in cancer and proposed a mechanism to explain the differences in energy metabolism between normal and cancer cells. The accumulated evidence indicates that heteroplasmy attributed to mtDNA mutations is linked to neurodegenerative diseases, aging, and cancer.

Currently, no convenient method exists to reduce the proportion of mutant mtDNA, which would be crucial for the treatment of heteroplasmy-attributed disorders and future stem-cell therapies. It has recently been discovered a novel and universal mechanism responsible for mtDNA inheritance, including restoration of homoplasmy from heteroplasmy, through recombination-driven mtDNA rolling-circle replication, which can be activated by an optimal level of reactive oxygen species (ROS) in human cells. ROS-stimulated mt-allele segregation via rolling-circle mtDNA replication may provide either mtDNA mutation-rich iPSCs, iPSCs with a lower proportion of mutant mtDNA in heteroplasmy, or iPSCs with wild-type mtDNA homoplasmy. iPSCs with high levels of mtDNA mutations may be a suitable source of cells for human mitochondrial disease modeling, and iPSCs with lower proportions of mutant mtDNA would ensure the safety of iPSCs upon differentiation into somatic cells for autologous transplantation. Endogenous ROS that act in mitochondrial signaling should not be regarded as risk factors for cellular metabolism.

We welcome Original Research, Methods, Reviews, Hypothesis and Theory, Perspectives and other article types.

The scope of this Research Topic may focus on the following specific themes:
1. The mechanisms for mtDNA replication, repair, and segregation during reprogramming, or in iPSCs.
2. Mitochondrial quality control such as mtDNA turnover processes by mitophagy, especially during iPSCs reprogramming
3. Roles of ROS from during reprogramming of iPSCs.
4. Roles of mitochondrial function during differentiation of iPSCs, and/or during reprogramming to generate iPSCs.
5. Analysis of mechanisms of action of chemical compounds using iPSCs.
6. mtDNA mutation-attributed disease modeling in iPSCs, or other stem cells.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

30 December 2020 Manuscript
29 January 2021 Manuscript Extension

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

30 December 2020 Manuscript
29 January 2021 Manuscript Extension

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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