Tsunami of ERIBA papers
They say good things come in waves, but on rare occasions they come in tsunami’s. In May 2016, a tsunami of papers from ERIBA researchers has been published. Time for an overview.
Technological developments in the past decade have enabled high-resolution measurements of various epigenetic marks at a genome‑wide scale. The application of these technologies to population studies is expanding rapidly. Recent measurements show that individuals within a population can vary substantially in their epigenomic patterns, and it is becoming increasingly clear that this variation may have important biomedical, agricultural and even evolutionary implications. However, the causes underlying this variation remain largely elusive. In their review “Genetic sources of population epigenomic variation” published in Nature Reviews Genetics on May 9, Aaron Taudt (PhD student, ERIBA), Maria Colomé-Tatché (Group Leader of Quantitative Epigentics, ERIBA) and Frank Johannes (Prof. in Population epigenetics and epigenomics, Technical University of Munich) summarize recent studies in a number of species and the role of genetic factors as a possible source of epigenomic variation. The review quantifies the proportion of the epigenome that is found to be under genetic control and highlights emerging insights into possible genetic regulatory mechanisms.
On May 16, the article titled “Bromodeoxyuridine does not contribute to sister chromatid exchange events in normal or Bloom syndrome cells“, was published in Nucleic Acids Research. The paper is a contribution from Niek van Wietmarschen, PhD student, and Peter Lansdorp, group leader of the ERIBA Genetic Instability Ageing Center. Their study shows that in contrast to results from previous studies, the exchange of genetic material between the identical copies of a single chromosome (Sister Chromatid Exchange, or “SCE” event) is not induced by culturing cells in the presence of bromodeoxyuridine (BrdU). SCEs are considered a sensitive indicator of DNA damage and genome instability and BrdU is used in the method to detect them. If the presence of BrdU would increase the number of SCEs, conclusions regarding the naturally occurring number of SCE events in a cell might be unreliable. For this paper, van Wietmarschen and Lansdorp used Strand-seq, a single cell sequencing method which was previously developed in the Lansdorp lab in Vancouver. With this method, the effect of BrdU on the number of SCEs occurring in cells was measured. The method was used on both normal cells and cells from patients with Bloom’s syndrome, which have a tenfold elevated level of SCEs. Based on their findings the authors conclude that BrdU does not induce SCE events, and that the observed number of SCEs is caused by DNA repair events that occur spontaneously in cells.
Peter Lansdorp, Scientific Director at ERIBA and the group leader of the Genetic Instability Ageing center was asked to write an editorial for the New England Journal of Medicine on a paper that describes a clinical intervention in patients with “telomere disorders”. These patients have very short telomeres and are at high risk of bone marrow failure. Treatment of such patients with anabolic steroids was found not just to slow down telomere attrition, but also results in lengthening of telomeres and improvement of blood counts associated with the telomere lengthening (“Danazol Treatment for Telomere Diseases” by Townsley et al.) NEJM felt that their readership would benefit from further explanation and commentary from Peter Lansdorp, a recognized expert in the telomere field. Methods to measure telomere length were developed in the Vancouver laboratory of Peter Lansdorp and telomere length measurements are offered by Repeat Diagnostics Inc., the leading clinical laboratory specializing in telomere length testing analysis founded by Peter Lansdorp. The resulting paper, “Telomeres on Steroids — Turning Back the Mitotic Clock?” describes the exciting findings of Townsley et al. which “provide food for thought about the role of telomeres and telomerase in hematopoietic stem cells”.
Single cell biology is a rapidly developing field. For this reason, the latest issue of Genome Biology is devoted to single cell biology featuring two ERIBA-studies. Both studies use single cell sequencing to quantify chromosome copy number in single cells, but in quite different settings. The first paper, ”Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies”, is a joint effort of Bjorn Bakker (laboratory of Genomic Instability in Development and Disease, with group leader Floris Foijer) and Aaron Taudt (laboratory of Quantitative Epigenetics, with group leader Maria Colomé-Tatché). Their paper describes the combination of a single-cell whole genome sequencing platform and a fully automated analysis pipeline (AneuFinder) that can quantify aneuploidy (an abnormal number of chromosomes) at the single cell level. Using this platform and AneuFinder software, Bakker and Taudt could carefully quantify chromosome copy numbers and heterogeneity within primary mouse and human tumors. Their analysis revealed that different tumors display different levels of intratumour heterogeneity, mostly higher than previously anticipated. These findings are important, as chromosome copy number heterogeneity previously remained undetected. It could be an important factor to consider when predicting the progression of a tumor and its potential response to treatment.
In the second Genome Biology paper “Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer’s disease neurons”, single-cell whole genome sequencing was used to study the neurons of normal individuals and patients with Alzheimer’s disease (AD). The paper, written by Hilda van den Bos from the ERIBA Genetic Instability Ageing Center (led by Peter Lansdorp), was published on May 31. The neurons of AD patients were studied to investigate the possible role of aneuploidy in AD proposed in earlier studies. The single cell sequencing method used was convincingly validated using cells from a Down’s syndrome patient. Very low levels (<1%) of aneuploidy were found in both normal neurons and neurons from AD patients making it very unlikely that abnormal chromosome numbers are at the heart of this devastating disease.
Congratulations to all contributors with these publications!
References:
Aaron Taudt, Maria Colomé-Tatché, Frank Johannes. (2016) Genetic sources of population epigenomic variation. Nature Reviews Genetics. http://dx.doi.org/10.1038/nrg.2016.45
Niek van Wietmarschen, Peter M. Lansdorp. (2016) Bromodeoxyuridine does not contribute to sister chromatid exchange events in normal or Bloom syndrome cells. Nucleic Acids Research. http://dx.doi.org/10.1093/nar/gkw422
Peter M. Lansdorp. (2016) Telomeres on Steroids — Turning Back the Mitotic Clock? New England Journal of Medicine. http://dx.doi.org/10.1056/NEJMe1602822
Bakker B, Taudt A, Belderbos ME, Porubsky D, Spierings DC, de Jong TV, Halsema N, Kazemier HG, Hoekstra-Wakker K, Bradley A, de Bont ES, van den Berg A, Guryev V, Lansdorp PM, Colomé-Tatché M, Foijer F. (2016) Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies. Genome Biology. http://dx.doi.org/10.1186/s13059-016-0971-7
van den Bos H, Spierings DC, Taudt AS, Bakker B, Porubský D, Falconer E, Novoa C, Halsema N, Kazemier HG, Hoekstra-Wakker K, Guryev V, den Dunnen WF, Foijer F, Tatché MC, Boddeke HW, Lansdorp PM. (2016) Single-cell whole genome sequencing reveals no evidence for common aneuploidy in normal and Alzheimer’s disease neurons. Genome Biology. http://doi.org/10.1186/s13059-016-0976-2
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