gms | German Medical Science

60. Jahrestagung der Deutschen Gesellschaft für Neuropathologie und Neuroanatomie (DGNN)

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie

26. - 28.08.2015, Berlin

Epigenetic analysis of induced pluripotent stem cells established from Parkinson’s disease patients

Meeting Abstract

  • corresponding author presenting/speaker Markus Schulze - Universitätsklinikum Regensburg, Abteilung für Neuropathologie, Regensburg, Germany
  • Beate Winner - FAU Erlangen-Nürnberg, Interdisciplinary Center for Clinical Research, Nikolaus-Fiebiger Center for Molecular Medicine, Erlangen, Germany
  • Jürgen Winkler - FAU Erlangen-Nürnberg, Interdisciplinary Center for Clinical Research, Nikolaus-Fiebiger Center for Molecular Medicine, Erlangen, Germany; FAU Erlangen-Nürnberg, Department of Molecular Neurology, Erlangen, Germany
  • author Markus Riemenschneider - Universitätsklinikum Regensburg, Abteilung für Neuropathologie, Regensburg, Germany
  • IPS Bavarian Research Network on induced pluripotent stem cells - Universitätsklinikum Regensburg, Abteilung für Neuropathologie, Regensburg, Germany; FAU Erlangen-Nürnberg, Interdisciplinary Center for Clinical Research, Nikolaus-Fiebiger Center for Molecular Medicine, Erlangen, Germany; FAU Erlangen-Nürnberg, Department of Molecular Neurology, Erlangen, Germany

Deutsche Gesellschaft für Neuropathologie und Neuroanatomie. 60th Annual Meeting of the German Society for Neuropathology and Neuroanatomy (DGNN). Berlin, 26.-28.08.2015. Düsseldorf: German Medical Science GMS Publishing House; 2015. Doc15dgnnP4

doi: 10.3205/15dgnn28, urn:nbn:de:0183-15dgnn288

Veröffentlicht: 25. August 2015

© 2015 Schulze et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Introduction: Parkinson’s disease (PD) is the second most common neurodegenerative disorder, characterized by the loss of dopaminergic neurons from the substantia nigra. Recently, epigenetic changes, e.g. aberrant miRNA expression patterns and hypomethylation of α-synuclein, have been linked to the development of the disease. As part of the ForIPS consortium our group analyses the epigenetic characteristics of patient derived fibroblasts and induced pluripotent stem cells (iPSCs).

Objectives: The goal of the ForIPS consortium is to gain a deeper understanding of the molecular alterations in chronic sporadic brain diseases using patient derived fibroblasts and iPS cells as a model system. The specific contribution of our working group is to analyze methylation, miRNA and mRNA patterns on a genome wide scale.

Materials & methods: Induced pluripotent stem cells were generated by the core project in Erlangen using the classical Yamanaka protocol. Small RNA and mRNA libraries were prepared for sequencing on an Illumina platform. In parallel, the methylation status of the DNA was analyzed by Reduced Representation Bisulfite Sequencing (RRBS).

Results: As expected, sequencing of iPSCs and fibroblasts generated fundamentally different profiles on the mRNA level, and the iPSCs showed strong overexpression of pluripotency associated genes. Moreover, the expression signatures within the ForIPS cohort showed high correlation with NGS-based expression profiles from other highly cited iPSC studies. Most interestingly, comparing fibroblasts from PD and control patients we detected several thousand differentially methylated regions, some of which remained differentially methylated even after reprogramming. Several differentially expressed transcripts were detected also on the mRNA level, with one of them being a known PD-associated gene.

Conclusion: Taken together, we generated high quality sequencing data suggesting the presence of PD-related epigenetic marks in peripheral tissues. The affected genes are valuable candidates for further functional characterization in our cellular model system and might bear the potential for diagnostic testing procedures to support an early detection of Parkinson’s disease.