A novel system for correcting large-scale chromosomal aberrations: ring chromosome correction via reprogramming into induced pluripotent stem cell (iPSC)
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Approximately 1 in 500 newborns are born with chromosomal abnormalities that include trisomies, translocations, large deletions, and duplications. There is currently no therapeutic approach for correcting such chromosomal aberrations in vivo or in vitro. When we attempted to produce induced pluripotent stem cell (iPSC) models from patient-derived fibroblasts that contained ring chromosomes, we found that the ring chromosomes were eliminated and replaced by duplicated normal copies of chromosomes through a mechanism of uniparental isodisomy (Bershteyn et al. 2014, Nature 507:99). The discovery of this previously unforeseen system for aberrant chromosome correction during reprogramming enables us for the first time to model and understand this process of cell-autonomous correction of ring chromosomes during human patient somatic cell reprograming to iPSCs. This knowledge could lead to a potential therapeutic strategy to correct common large-scale chromosomal aberrations, termed “chromosome therapy”.
KeywordsRing chromosomes Large-scale aberration Induced pluripotent stem cells (iPSCs) Compensatory uniparental disomy (UPD) Genome editing Chromosome therapy
Induced pluripotent stem cells
Compensatory uniparental disomy
Miller Dieker Syndrome
Engineered zinc finger nucleases
Transcription activator-like effector nucleases
Clustered regularly interspaced short palindromic repeats
We thank Justine Ngo for the helpful discussion and comments on the manuscript.
Compliance with ethical standards
This work was supported by a grant from Ring 14 International.
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
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