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Mitochondrial Genome Mutates When Reprogrammed
Mutations in the mitochondrial
genome of iPS cells;
© MPI for Molecular Genetics
However, these promising cells are also associated with certain risks. Disease-causing mutations can also arise during the reprogramming of the body cells. A cooperative research study involving two research groups from the Max Planck Institute for Molecular Genetics in Berlin has now carried out a search for mutations in the mitochondrial genome of iPS cells. James Adjaye’s research group recently discovered that the mitochondria rejuvenate in the course of reprogramming.
Working in cooperation with Bernd Timmermann’s Next Generation Sequencing research group, Adjaye’s team has succeeded in showing that genetic mutations exist in the mitochondrial genome of all reprogrammed cells that were not present in the original cells. The amount of mutations varies significantly between the individual iPS cells examined. In all cases, the changes did not involve large-scale rearrangements but rather modifications of single letters in the genetic code.
“The mitochondrial genome undergoes random reorganisation during reprogramming,” explains James Adjaye. “Cell lines can arise in the process that carries disease-causing mutations. Genetic mutations in the mitochondrial genome may be responsible, for example, for various metabolic disorders, nervous diseases, tumours and post-transplant rejection reactions. Therefore, it is essential that cell lines intended for clinical use be tested for such mutations,” he adds.
For their study, the scientists generated iPS cells from human skin cells (fibroblasts). Based on a standard procedure, they used viruses as a vehicle for the infiltration of certain regulator genes into the skin cells. These genes, which are usually only active in the embryo, transpose the cell back to a juvenile state. As a result it gains the potential to differentiate into almost all of the cell types found in the human body, in other words, it becomes pluripotent.
As the researchers discovered, the observed mitochondrial mutations had no effects on the outcome of the reprogramming process: the reprogrammed iPS cells behaved like normal embryonic stem cells and their metabolism did not appear to have been impaired.
MEDICA.de; Source: Max Planck Society