Study of genetic stability of induced pluripotent stem cells intended for modeling hereditary diseases

   Background. Genetic stability of model cell cultures is a fundamental prerequisite for ensuring the validity and reproducibility of experimental results. Induced pluripotent stem cells (iPSCs) are inherently prone to developing spontaneous genetic abnormalities. Thus, monitoring the genetic stability of iPSCs every 5–10 passages during culture expansion is essential. Optimizing methods for routine analysis of iPSC genetic stability requires an in-depth investigation of the spectrum of abnormalities characteristic of these cells, along with their structural features and potential functional implications.

   Aim: to identify and analyze genomic anomalies in iPSC cultures derived from Russian laboratories.

   Methods. iPSC lines (n = 66), derived in five laboratories from biological material sourced from six healthy donors and 27 patients diagnosed with genetic diseases (15 nosologies), were analyzed using karyotyping techniques. Identified karyotype anomalies were validated through fluorescent in situ hybridization, spectral karyotyping, and SNP microarray analysis.

   Results. Karyotype abnormalities were observed in 23.6 % of the samples, including trisomy of chromosomes 20 and 8, isochromosome 20q, and structural rearrangements involving chromosomes 1, 2, 8, 15, and 18. Recurrent gains of chromosome segments 1q and 20q accounted for 69 % of the detected aberrations.

   Conclusions. The structure and frequency of karyotype abnormalities in iPSC lines derived from Russian laboratories are consistent with previously reported data from studies of iPSC lines in international collections. The high prevalence of recurrent aberrations highlights the potential for implementing targeted analysis of genetic stability of cell lines.

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