ArticleStem cell reports2021
iPSC culture expansion selects against putatively actionable mutations in the mitochondrial genome.
Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- Long-read sequencing enables high-accuracy mitochondrial heteroplasmy detection in Parkinson's disease.BMC genomics · 2026Article
- Engineering Mitochondrial Biogenesis in iPSC-CMs: CRISPR-Guided Approaches for Advanced Cardiomyocyte Development.Journal of cardiovascular development and disease · 2026Review
- Increased mitochondrial mutation heteroplasmy induces aging phenotypes in pluripotent stem cells and their differentiated progeny.Aging cell · 2025Article
- Association of Inflammatory Mediators with Mitochondrial DNA Variants in Geriatric COVID-19 Patients.Aging and disease · 2024Article
- Metabolic control of induced pluripotency.Frontiers in cell and developmental biology · 2023Review
- The Mitochondrial Genome in Aging and Disease and the Future of Mitochondrial Therapeutics.Biomedicines · 2022Review
- Modelling Mitochondrial Disease in Human Pluripotent Stem Cells: What Have We Learned?International journal of molecular sciences · 2021Review
- Mitochondrial DNA Dynamics in Reprogramming to Pluripotency.Trends in cell biology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic application of induced pluripotent stem cell (iPSC) derivatives requires comprehensive assessment of the integrity of their nuclear and mitochondrial DNA (mtDNA) to exclude oncogenic potential and functional deficits. It is unknown, to which extent mtDNA variants originate from their parental cells or from de novo mutagenesis, and whether dynamics in heteroplasmy levels are caused by inter- and intracellular selection or genetic drift. Sequencing of mtDNA of 26 iPSC clones did not reveal evidence for de novo mutagenesis, or for any selection processes during reprogramming or differentiation. Culture expansion, however, selected against putatively actionable mtDNA mutations. Altogether, our findings point toward a scenario in which intracellular selection of mtDNA variants during culture expansion shapes the mutational landscape of the mitochondrial genome. Our results suggest that intercellular selection and genetic drift exert minor impact and that the bottleneck effect in context of the mtDNA genetic pool might have been overestimated.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.