iPSC reprogramming-mediated aneuploidy correction in autosomal trisomy syndromes
Silvia Natsuko Akutsu1, Tatsuo Miyamoto1, Daiju Oba2
1Department of Genetics and Cell Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan.
Plos One
|March 10, 2022
Summary
Researchers observed spontaneous correction of trisomy to disomy in induced pluripotent stem cells (iPSCs) derived from patients with Down syndrome and other autosomal aneuploidies. This trisomy rescue involves the random loss of an extra chromosome during reprogramming, offering insights into karyotype correction mechanisms.
Area of Science:
- Genetics
- Cell Biology
- Developmental Biology
Background:
- Autosomal aneuploidies like Trisomy 21, 18, and 13 are major human disorders causing congenital malformations.
- Current treatments for aneuploidies are limited, highlighting the need for novel therapeutic strategies.
- Trisomy-biased chromosome loss during induced pluripotent stem cell (iPSC) reprogramming offers a potential avenue for karyotype correction.
Purpose of the Study:
- To investigate the mechanism of trisomy rescue during the early stages of cell reprogramming.
- To evaluate the spontaneous correction of trisomy to disomy in iPSCs derived from various trisomy syndromes.
Main Methods:
- Reprogramming of skin fibroblasts from patients with Trisomy 21, 18, 13, and 9 into iPSCs.
- Molecular cytogenetic techniques to analyze the genomes of individual iPSC colonies.
- Single nucleotide polymorphism (SNP) analysis to determine the genetic makeup of trisomy-rescued clones.
Main Results:
- Spontaneous correction from trisomy to disomy was observed in iPSC lines from each trisomy syndrome studied.
- Three distinct chromosomal combinations were identified in isogenic trisomy-rescued iPSC clones.
- SNP analysis indicated the loss of one extra chromosome, rather than simultaneous loss and duplication, leading to disomic cells.
Conclusions:
- Trisomy rescue during iPSC reprogramming involves random chromosome loss and selection for disomic cells.
- This phenomenon is analogous to karyotype correction observed in early preimplantation embryos.
- Findings provide insights into autonomous karyotype correction mechanisms and potential applications in aneuploidy research.
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