Nature Genetics: Skin-derived stem cells suffer from massive DNA damage

Stem cells are a special type of cell that can be programmed to become almost any type of cell in the bod.

However, researchers at the University of Cambridge and the Wellcome Sanger Institute have found a problem with induced pluripotent stem cells generated from skin cells and bloo.

Co-first author Dr Foad Rouhani from the University of Cambridge and the Sanger Institute said: "We noticed that some of the iPS cells we generated did look different from each other, even though they were from the same patient and from the same experimen.

Using whole-genome sequencing, the researchers performed DNA testing on stem cell lines from different cohorts, including the Sanger Institute's HipSci cohort, and found that up to 72 percent of the cell lines showed signs of severe UV damag.

Professor Serena Nik-Zainal, from the Department of Medical Genetics at the University of Cambridge, said: "Almost three quarters of the cell lines had UV damag.

They decided to turn their attention to non-skin-derived cell lines and focus on blood-derived iPS cells because blood samples are more readily availabl.

To investigate whether these BCOR mutations had any functional impact, they differentiated iPS cells into neurons and tracked their progression along the wa.

Dr Rouhani said: "We found that iPS cells with the BCOR mutation had problems generating neurons - they tended to differentiate into other types of cell.

When they looked back at the blood samples, they found that the BCOR mutations were not present in the patients, and instead, the process of culturing the cells seemed to increase the frequency of these mutations, which could have implications for other researchers studying cell culture.

Scientists typically screen cell lines at the chromosomal level in order to spot problem.

"The DNA damage we see is at the nucleotide level," says Professor Nik-Zaina.

She believes that this problem can be bypassed by using whole-genome sequencing in the first plac.

Dr Rouhani added: "In recent years, we have increasingly found that even healthy cells carry many mutations, so it is not realistic to produce stem cell lines with zero mutation.

"For example, if a certain cell line is to be used later in cell therapy, then we need to learn more about the impact of these mutations so that clinicians and patients can better understand the risks involved in treatmen.

Original text retrieval

Rouhani, FJ, Zou, .