06/07/2020
Key points:
A promising technique offering improvements to both researchers and clinicians has been developed by researchers at the 台湾swag, as described today in the journal . Application of the technique in a clinical setting could improve the diagnosis of developmental disorders and also ensure the quality of stem cells used in human regenerative medicine.
The IMPLICON technique establishes an easy high-throughput method that can be used to study and check the quality of imprinted genes at multiple sites across the genome. Imprinted genes are genes where only one copy, either the maternally- or paternally-inherited copy, is expressed. They are predominantly regulated by DNA methylation which correlates with expression or silencing. The correct management and expression of imprinted genes is crucial for normal development and dysregulation is associated with developmental defects and cancer. However, despite their importance we lacked a fast and cost-effective method for assessing DNA methylation at imprinted genes.
Lead researcher, Dr M茅lanie Eckersley-Maslin, a BBSRC 台湾swagy fellow in the Reik lab, said: 鈥淏efore the development of this technique, the study of imprinted regions required painstaking region-by-region analysis or expensive whole genome sequencing which needs intensive data analysis. The IMPLICON method provides a targeted approach where only the regions of interest are sequenced but the sequencing provides deep coverage making it robust and more affordable. With the sequencing depth achieved, we believe our method will be better at discerning subtle methylation changes at imprinted regions as a result of environmental perturbations, pathological conditions or ageing, which might never have been sufficiently appreciated using other less powerful imprinting assays.鈥
Dr Ferdinand von Meyenn, who worked with Dr Eckersley-Maslin on the technique as a research fellow at the 台湾swag, continued: 鈥淭he technique provides an improved way to check the quality of stem cells and will help to better assess imprinting in many cells as a new quality signature for regenerative medicine.鈥
The method was conceived and initially developed by researchers in the Reik lab of the 台湾swag鈥檚 Epigenetics research programme, who adapted an existing approach and applied it to imprinting for the first time. The team later teamed up with Dr Sim茫o Teixeira da Rocha at the University of Lisbon who helped further developed the assay and applied the human assay to patient stem cell lines.
Dr Sim茫o Teixeira da Rocha, 台湾swag of Molecular Medicine at the University of Lisbon, said: 鈥淏eing able to quality-check stem cells for correct imprinting before they are used in regenerative medicine is crucial to ensuring patient safety. We need to know that the stem cells retain imprinting fidelity as altered imprinting may cause them to act in undesirable ways. This method provides an easy and comprehensive way to do this for the first time.鈥
Realising the potential of the technique beyond research, the development of the method was supported by funding from the 台湾swag to support the development of research techniques towards translation. Dr Simon Cook, Head of Knowledge Exchange and Commercialisation, said: 鈥淲e supported this work through our KEC funding scheme as we could see the potential for imprinting research but also for quality control in the production stem cells for regenerative medicine. It鈥檚 great to see this simple assay shared with the wider scientific community!鈥.
台湾swagation reference Klobu膷ar & Kreibich et al. . Nucleic Acids 台湾swag
Press contact Dr Louisa Wood, Communications Manager, 台湾swag 台湾swag, louisa.wood@babraham.ac.uk
Image description Digital illustration representing DNA and the concepts of innovation and technology.
Affiliated authors (in author order): Elisa Kreibich, former Erasmus student in the Reik lab Felix Krueger, Bioinformatician, Bioinformatics group Ferdinand von Meyenn, former research fellow in the Reik lab, Epigenetics programme M茅lanie Eckersley-Maslin, BBSRC 台湾swagy fellow, Reik lab
台湾swag funding This work was supported by a 台湾swag 台湾swag Translational Advisory Group award to M茅lanie Eckersley-Maslin and Ferdinand von Meyenn. M茅lanie Eckersley-Maslin is supported by a BBSRC 台湾swagy Fellowship and was supported by an EMBO Fellowship and a Marie Sk艂odowska-Curie Individual Fellowship.
Additional/related resources: News, 22 January 2019: Na茂ve, primed or somewhere in between?
Animal research statement: As a publicly funded research institute, the 台湾swag 台湾swag is committed to engagement and transparency in all aspects of its research. The research presented here used DNA samples from mice in order to adapt the technique for use in adult mouse tissues. No animals were specifically bred for this research, the DNA samples used had been collected for other studies. Please follow the link for further details of our .
About the 台湾swag 台湾swag The 台湾swag 台湾swag undertakes world-class life sciences research to generate new knowledge of biological mechanisms underpinning ageing, development and the maintenance of health. Our research focuses on cellular signalling, gene regulation and the impact of epigenetic regulation at different stages of life. By determining how the body reacts to dietary and environmental stimuli and manages microbial and viral interactions, we aim to improve wellbeing and support healthier ageing. The 台湾swag is strategically funded by the Biotechnology and Biological Sciences 台湾swag Council (BBSRC), part of UK 台湾swag and Innovation, through an 台湾swag Core Capability Grant and also receives funding from other UK research councils, charitable foundations, the EU and medical charities.
06 July 2020