Simão Teixeira da Rocha, senior researcher in the Maria Carmo-Fonseca group at the iMM, together with Mélanie Eckersley-Maslin, associated with the Babraham Institute (United Kingdom), developed a new technique that allows measuring parental imprinting fidelity in different biological contexts. The results, now published in the prestigious scientific journal Nucleic Acids Research, can improve the diagnosis of developmental disorders and also guarantee the quality of stem cells used in regenerative medicine.
Parental imprinting determines that for some genes only one of the two copies inherited (by the father or mother) is expressed. Normal development in the embryo depends on the correct dosage of these genes. Deregulation of this activity is associated with developmental problems, such as Angelman's syndrome, and is seen in cancer cells. However, despite its importance, a fast and economical method for evaluating these epigenetic DNA signatures was lacking.
"The IMPLICON technique is an easy and inexpensive method that can be used to study and verify the quality of these epigenetic signatures in various locations in the genome with unprecedented resolution", explains Simão Teixeira da Rocha, one of those responsible for this study: “Before the development of this technique, the study of these regions needed a thorough and individual analysis or expensive sequencing methods that required an exhaustive analysis. The IMPLICON method offers a targeted approach, in which only the regions of interest are sequenced, but the process provides deep coverage, making it robust and more accessible. We believe that, this way, it will be more effective to analyse subtle changes in these “epigenetic signatures” as a result of environmental disturbances, pathological conditions or ageing, which could never have been sufficiently observed using other techniques”, adds Mélanie Eckersley-Maslin, a researcher also responsible for the work.
The method was initially conceived and developed by researchers from the Wolf Reik laboratory (Babraham Institute), who adapted an existing approach and applied it to parental imprinting. The team allied with Simão Teixeira da Rocha, who helped to optimize the method and applied the test to stem cell lines of patients with Angelman syndrome.
Researcher Simão Teixeira da Rocha underlines: “Being able to verify that stem cells have the correct parental imprinting pattern is essential to guarantee the quality and safety of the use of these cells in regenerative medicine”.
Scientific article: Tajda Klobučar, Elisa Kreibich, Felix Krueger, Maria Arez, Duarte Pólvora-Brandão, Ferdinand von Meyenn, Simão Teixeira da Rocha*, Melanie Eckersley-Maslin*. (2020) IMPLICON: an ultra-deep sequencing method to uncover DNA methylation at imprinted regions. Nucleic Acids Research, gkaa567, https://doi.org/10.1093/nar/gkaa567