ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Reprogramming enriches for somatic cell clones with small-scale mutations in cancer-associated genes.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 17 citations in OpenAlex.
- Review
- Urine-derived induced pluripotent stem cells for non-invasive diagnosis of bladder cancer.Journal of Cancer · 2026Review
- Rejuvenation of white adipose tissue in a longitudinal heterochronic transplantation model.bioRxiv : the preprint server for biology · 2025Article
- Cell-based regenerative and rejuvenation strategies for treating neurodegenerative diseases.Stem cell research & therapy · 2025Review
- High prevalence of acquired cancer-related mutations in 146 human pluripotent stem cell lines and their differentiated derivatives.Nature biotechnology · 2024Article
- Article
- Review
- The long and winding road of reprogramming-induced rejuvenation.Nature communications · 2024Review
- Targeted biallelic integration of an inducible Caspase 9 suicide gene in iPSCs for safer therapies.Molecular therapy. Methods & clinical development · 2022Article
- The Tumorigenic Potential of Human Pluripotent Stem Cells.Stem cells translational medicine · 2022Article
- iPSC culture expansion selects against putatively actionable mutations in the mitochondrial genome.Stem cell reports · 2021Article
- Review
- Review
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cellular therapies based on induced pluripotent stem cells (iPSCs) come out of age and an increasing number of clinical trials applying iPSC-based transplants are ongoing or in preparation. Recent studies, however, demonstrated a high number of small-scale mutations in iPSCs. Although the mutational load in iPSCs seems to be largely derived from their parental cells, it is still unknown whether reprogramming may enrich for individual mutations that could lead to loss of functionality and tumor formation from iPSC derivatives. 30 hiPSC lines were analyzed by whole exome sequencing. High accuracy amplicon sequencing showed that all analyzed small-scale variants pre-existed in their parental cells and that individual mutations present in small subpopulations of parental cells become enriched among hiPSC clones during reprogramming. Among those, putatively actionable driver mutations affect genes related to cell-cycle control, cell death, and pluripotency and may confer a selective advantage during reprogramming. Finally, a short hairpin RNA (shRNA)-based experimental approach was applied to provide additional evidence for the individual impact of such genes on the reprogramming efficiency. In conclusion, we show that enriched mutations in curated onco- and tumor suppressor genes may account for an increased tumor risk and impact the clinical value of patient-derived hiPSCs.
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