iPSC Models of Ring Chromosomes, Genome Editing, and Chromosome Therapy

Induced pluripotent stem cells (iPSCs) are beneficial for studying of chromosomal diseases, including ring chromosomes (RCs), because iPSCs can be differentiated to various cell types, some of which are difficult to access in vivo. Patient-derived iPSCs are an infinite source of cells that can be genetically edited, and used for disease modeling, pathogenesis studies, as well as for gene therapy. Here, we review the studies of patient-derived iPSCs carrying a RC and consider mitotic instability of RC in pluripotent state. We also discuss normalization of the iPSCs karyotype through a loss of the RC due to its mitotic instability and a compensatory rescue by replicating the normal homolog, which has been proposed as an approach for karyotype correction named “chromosome therapy.” Some issues of difference in RC mitotic stability between somatic and pluripotent cells are considered, as well as possible reasons for diversity of RC stability between long-term cultures of isogenic lines. We also review the stability of small supernumerary marker or ring chromosomes (sSMC/sSRCs) and the appearance and stabilization of RC in pluripotent cells. Overall, patient-derived iPSCs seems to be a promising tool for studies of RCs in human cells.