Telomeres are the protective caps at chromosome ends. In adult cells, telomeres shorten each time a cell divides and this contributes to ageing and cancer. Pluripotent stem cells, however, are specialised cells that exist in the earliest days of development. These pluripotent cells do not age and have the ability to turn into any type of adult cell.
The surprise finding, published today in Nature, shows that telomeres in pluripotent stem cells are protected very differently than telomeres in adult tissues.
This upends 20 years of thinking on how stem cells protect their DNA, said Associate Professor Tony Cesare, from the University of Sydneys Faculty of Medicine and Health, who is Head of the Genome Integrity Unit at Childrens Medical Research Institute (CMRI) and co-leader of a research team that collaborated on this research.
In adult cells, a protein called TRF2 is essential because it arranges DNA at the chromosome end into a telomere-loop structure. Removing TRF2 from adult cells causes the chromosomes to become stitched together into one long string, which is incompatible with life.
To the researchers astonishment, removing TRF2 from pluripotent stem cells did almost nothing. The chromosomes were normal, the telomere-loops remained, and the cells divided as if nothing happened. Telomeres are therefore protected differently in pluripotent stem cells and adult tissues.
This unexpected finding has major implications for research on ageing, human development, regenerative medicine, and cancer. Previously, researchers expected fundamental mechanisms that protected DNA would be the same in all tissues. This now appears to be incorrect.
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