Key Points:
- In a study, 72% of stem cell lines in different cohorts showed signs of major UV damage.
- Some samples had an enormous number of mutations, even more than typically find in tumors.
- The study authors say it is essential to use whole genome sequencing to look in detail for errors at the outset of stem cell research.
Increasingly, researchers are turning to stem cells to develop new cell-based therapies, or reprogramming them to grow into other kinds of cells, such as nerve cells to replace those lost to neurodegenerative diseases like Parkinson’s.
Originally, stem cells were derived from embryos, but it is now possible to derive stem cells from adult skin cells. These induced pluripotent stem cells (iPSCs) have now been generated from a range of tissues. However, in a new study published in Nature Genetics, researchers have discovered a problem with stem cell lines derived from both skin cells and blood.
When they examined the genomes of the stem cell lines in detail, they found that nearly three quarters carried substantial damage to their DNA that could compromise their use both in research and cell-based therapies. Their findings represent the largest genetic study to date of iPSCs.
Using whole genome sequencing, the research team discovered as many as 72% of the stem cell lines in different cohorts showed signs of major UV damage. Additionally, the scientists found that at least one-quarter of blood-derived iPSCs carried mutations in a gene called BCOR, an important gene in blood cancers.
To investigate whether these BCOR mutations had any functional impact, they differentiated the iPSCs and turned them into neurons, tracking their progress along the way. The research team discovered that the BCOR mutations were not present within the patient: instead, the process of culturing cells appears to increase the frequency of these mutations, which may have implications for other researchers working with cells in culture.
“The DNA damage that we saw was at a nucleotide level,” said Serena Nik-Zainal from the Department of Medical Genetics at the University of Cambridge. “If you think of the human genome as like a book, most researchers would check the number of chapters and be satisfied that there were none missing. But what we saw was that even with the correct number of chapters in place, lots of the words were garbled.”
Fortunately, says Nik-Zainal, there is a way around the problem: using whole genome sequencing to look in detail for the errors at the outset.
“In recent years we have been finding out more and more about how even our healthy cells carry many mutations and therefore it is not a realistic aim to produce stem cell lines with zero mutations,” said Foad Rouhani, who carried out the work while at the University of Cambridge and the Wellcome Sanger Institute. “The goal should be to know as much as possible about the nature and extent of the DNA damage to make informed choices about the ultimate use of these stem cell lines.”
Information provided by University of Cambridge.