Stem cells protect chromosome ends to prevent ageing

Chromosome ends are protected differently in stem cells compared to adult cells.

Two teams have independently shown how stem cells protect their chromosome ends, known as telomeres. These specialised structures protect our DNA and safeguard healthy cell division. In adult stem cells, known as somatic cells, telomeres shorten every time a cell divides, which contributes to ageing and cancer. In contrast, pluripotent stem cells do not age and have the ability to turn into any type of adult cell. Surprisingly, these two teams of scientists have shown that telomeres in pluripotent stem cells are protected very differently when compared to telomeres in somatic cells.

The first collaboration was formed of scientists from the Genome Integrity Unit, Children's Medical Research Institute (CMRI) at the University of Sydney, Australia and scientists at the Francis Crick Institute, London. Dr Simon Boulton, from the Francis Crick Institute, and corresponding author of the first Nature paper said 'Rather than totally contradicting years of telomere research, our study refines it in a very unique way. Basically, we've shown that stem cells protect their chromosome ends differently to what we previously thought'.

A key protein in the protection of telomeres in somatic cells is TRF2, which stabilises a loop structure, called a telomere-loop, or t-loop. It is this loop which protects the end of the chromosome. When the TRF2 protein is removed from somatic cells the t-loop does not form, resulting in the telomeres fusing together and subsequent cell death. However, these studies have shown that this is redundant in the healthy division of embryonic stem cells, which are pluripotent.

Dr Eros Lazzerini Denchi, from the National Cancer Institute, Bethesda, Maryland, and corresponding author of the second Nature paper said 'We expected the cells to be really sick, but instead they were totally fine'.

Both teams have shown that mouse embryonic stem cells, where the TRF2 gene is removed, are still able to form t-loops and the protection of telomeres is nearly completely unaffected. The studies also confirmed that the loops themselves must form part of the protective mechanism in stem cells where this had only been suggested in previous studies.

It is understood that as these stem cells differentiate into somatic cells, TRF2-linked t-loop formation becomes essential for this mechanism supporting healthy cell division. From this the scientists inferred that stem cells and somatic cells protect their chromosomal ends in different ways.

Dr Boulter added 'A better understanding of how telomeres work, and how they protect the ends of chromosomes could offer crucial insights into the underlying processes that lead to premature ageing and cancer.'

Dr Anthony Cesare, associate professor at CMRI concluded that the discovery was important for understanding stem cells, which are increasingly being used to develop treatments for many diseases.