Cell's unique mutations used to trace history back to its origins in the embryo
Researchers have developed new methods to trace the life history of individual cells back to their origins in the fertilised egg. By looking at the copy of the human genome present in healthy cells, they were able to build a picture of each cell's development from the early embryo on its journey to become part of an adult organ.
During the life of an individual, all cells in the body develop mutations, known as somatic mutations, which are not inherited from parents or passed on to offspring. These somatic mutations carry a coded record of the lifetime experiences of each cell.
By looking at the numbers and types of mutations in a cell's DNA, researchers were able to assess whether the cell had divided a few times or many times and detect the imprints, known as signatures, of the processes of DNA damage and repair that the cells had been exposed to during the life of the individual. Furthermore, comparing each cell's mutations with those of other cells in the body enabled scientists to map out a detailed tree of development from the fertilised egg.
"With this novel approach, we can peer back into an organism's development," says Dr Sam Behjati, first author from the Wellcome Trust Sanger Institute. "If we can better understand how normal, healthy cells mutate as they divide over a person's lifetime, we will gain a fundamental insight into what can be considered normal and how this differs from what we see in cancer cells."
The team looked at mouse cells from the stomach, small bowel, large bowel and prostate. The single cells were grown to produce enough DNA to be sequenced accurately. Eventually, single-cell sequencing technology will develop so that this type of experiment can be conducted using just one cell. However, the tiny amounts of DNA in single cells mean that mutation data are not currently precise enough to reconstruct accurate lineages.
The researchers recorded differences in the numbers of mutations in cells from the different tissues studied, likely attributable to differences in rates of cell division. Moreover, different patterns of mutation were found in cells from different tissues, suggesting that they have been exposed to different processes of DNA damage and repair, reflecting different lifetime experiences.
This experiment used healthy mice. If mutation rates are similar in human cells, these techniques could be used to provide an insight into the life histories of normal human cells.
"The adult human body is composed of 100 million million cells, all of which have originated from a single fertilised egg," says Professor Mike Stratton, senior author and Director of the Sanger Institute. "Much more extensive application of this approach will allow us to provide a clear picture of how adult cells have developed from the fertilised egg. Furthermore, by looking at the numbers and types of mutation in each cell we will be able to obtain a diary, writ in DNA, of what each healthy cell has experienced during its lifetime, and then explore how this changes in the range of human diseases."
Notes to Editors
Behjati et al. (2014) Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature DOI: 10.1038/nature13448
Please see the paper for a full list of participating centres.
The Hubrecht Institute for Developmental Biology and Stem Cell Research focuses on developmental biology and stem cells at the organismal, cellular, genetic, genomic and proteomic level. Basic insight into development and into stem cells will provide insight into (human) disease, such as cancer. The Hubrecht Institute is affiliated with the University Medical Center Utrecht and has close connections with the Utrecht University. http://www.hubrecht.eu/
The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease. http://www.sanger.ac.uk
The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests. http://www.wellcome.ac.uk
Mark Thomson | Eurek Alert!
Another piece of Ebola virus puzzle identified
17.01.2019 | Texas Biomedical Research Institute
New scale for electronegativity rewrites the chemistry textbook
17.01.2019 | Chalmers University of Technology
World first experiments on sensor that may revolutionise everything from medical devices to unmanned vehicles
The new sensor - capable of detecting vibrations of living cells - may revolutionise everything from medical devices to unmanned vehicles.
Dead and alive at the same time? Researchers at the Max Planck Institute of Quantum Optics have implemented Erwin Schrödinger’s paradoxical gedanken experiment employing an entangled atom-light state.
In 1935 Erwin Schrödinger formulated a thought experiment designed to capture the paradoxical nature of quantum physics. The crucial element of this gedanken...
Cellulose obtained from wood has amazing material properties. Empa researchers are now equipping the biodegradable material with additional functionalities to produce implants for cartilage diseases using 3D printing.
It all starts with an ear. Empa researcher Michael Hausmann removes the object shaped like a human ear from the 3D printer and explains:
The phenomenon of so-called superlubricity is known, but so far the explanation at the atomic level has been missing: for example, how does extremely low friction occur in bearings? Researchers from the Fraunhofer Institutes IWM and IWS jointly deciphered a universal mechanism of superlubricity for certain diamond-like carbon layers in combination with organic lubricants. Based on this knowledge, it is now possible to formulate design rules for supra lubricating layer-lubricant combinations. The results are presented in an article in Nature Communications, volume 10.
One of the most important prerequisites for sustainable and environmentally friendly mobility is minimizing friction. Research and industry have been dedicated...
Just in time for Christmas, a Mars-analogue mission in Morocco, coordinated by the Robotics Innovation Center of the German Research Center for Artificial Intelligence (DFKI) as part of the SRC project FACILITATORS, has been successfully completed. SRC, the Strategic Research Cluster on Space Robotics Technologies, is a program of the European Union to support research and development in space technologies. From mid-November to mid-December 2018, a team of more than 30 scientists from 11 countries tested technologies for future exploration of Mars and Moon in the desert of the Maghreb state.
Close to the border with Algeria, the Erfoud region in Morocco – known to tourists for its impressive sand dunes – offered ideal conditions for the four-week...
16.01.2019 | Event News
14.01.2019 | Event News
12.12.2018 | Event News
17.01.2019 | Physics and Astronomy
17.01.2019 | Materials Sciences
17.01.2019 | Information Technology