New mutations in iPS cells are mainly concentrated in non-transcriptional regions

October 10, 2017, RIKEN

Induced pluripotent stem cells—stem cell-like cells that have been reprogrammed from normal body cells—are a promising avenue of regenerative medicine, and are currently being tested in several clinical studies. However, there are concerns that the mutations that arise in these cells during their generation could potentially cause problems in transplant patients, in particular malignancies. Consequently, researchers are keen to understand the nature of the mutations that arise in these cells.

Now, in research published in Cell Reports, a team from the RIKEN Preventive Medicine and Diagnosis Innovation Program and other institutes has some potentially comforting news. By performing genomic analysis on both mouse and human iPS , they found that unlike disease-causing single nucleotide polymorphisms, the found in iPS cells tend to be concentrated into non-transcribed areas of the genome between genes. They also showed that the new mutations that arise in iPS cells are likely caused by oxidative stress, and that this seems to explain why they are concentrated in certain regions.

The specific areas where the new mutations tend to be found—called "lamina-associated domains"—are located on the outer edge of the cell's nucleus, in the membrane that separates the nucleus from the cytoplasm. These areas are characterized by condensed chromatin, and are sensitive to the oxidative damage released from mitochondria. It is known that mutations tend to occur differently in different parts of the genome, depending on a number of factors including the source of the damage, the accessibility of DNA repair mechanisms and the "chromatin status," which refers to how tightly the DNA is wrapped.

According to Yasuhiro Murakawa of the RIKEN Preventive Medicine and Diagnosis Innovation Program and the RIKEN Center for Life Science Technologies (CLST), who led the group, "In this study we found that though there are many mutations that arise during reprogramming, many of them are in transcriptionally repressed lamina-associated domains, and it is tempting to speculate that this means that they will not lead to adverse effects." The researchers also noted that most of the non-synonymous—meaning that the mutation leads to an actual change in a protein—mutations were not those found in a catalog of cancer-related mutations, so were essentially new mutations that still need to be investigated.

Murakawa says, "This study has given us insights into the broad mutational landscape of iPS cells, and it will give us a framework for looking at variations in iPS genomes. This will help us in the quest to develop new therapies."

Explore further: Test run finds no cancer risk from stem cell therapy

More information: Cell Reports (2017). DOI: 10.1016/j.celrep.2017.09.060

Related Stories

Mitochondrial genome mutates when reprogrammed

July 28, 2011

Induced pluripotent stem cells (iPS cells) are truly talented multi-taskers. They can reproduce almost all cell types and thus offer great hope in the fight against diseases like Alzheimer's and Parkinson's. However, it would ...

Recommended for you

Scientists find evidence of 27 new viruses in bees

June 20, 2018

An international team of researchers has discovered evidence of 27 previously unknown viruses in bees. The finding could help scientists design strategies to prevent the spread of viral pathogens among these important pollinators.

The cells that control the formation of fat

June 20, 2018

Fat cells, or adipocytes, are at the center of nutritional and metabolic balance. Adipogenesis—the formation of mature fat cells from their precursor cells—has been linked to obesity and related health problems such as ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.