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NPJ Schizophr. 2017 Jan 23;3:6. doi: 10.1038/s41537-016-0006-0. eCollection 2017.

DNA methylation in schizophrenia in different patient-derived cell types.

NPJ schizophrenia

Alejandra M Vitale, Nicholas A Matigian, Alexandre S Cristino, Katia Nones, Sugandha Ravishankar, Bernadette Bellette, Yongjun Fan, Stephen A Wood, Ernst Wolvetang, Alan Mackay-Sim

Affiliations

  1. Griffith Institute for Drug Discovery, Griffith University, Nathan, QLD Australia.
  2. Instituto de Biologia y Medicina Experimental-IBYME-CONICET, Buenos Aires, Argentina.
  3. The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD Australia.
  4. Queensland Centre for Medical Genomics, Institute for Molecular Bioscience, The University of Queensland, St Lucia, Brisbane, QLD Australia.
  5. Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD Australia.

PMID: 28560252 PMCID: PMC5441549 DOI: 10.1038/s41537-016-0006-0

Abstract

DNA methylation of gene promoter regions represses transcription and is a mechanism via which environmental risk factors could affect cells during development in individuals at risk for schizophrenia. We investigated DNA methylation in patient-derived cells that might shed light on early development in schizophrenia. Induced pluripotent stem cells may reflect a "ground state" upon which developmental and environmental influences would be minimal. Olfactory neurosphere-derived cells are an adult-derived neuro-ectodermal stem cell modified by developmental and environmental influences. Fibroblasts provide a non-neural control for life-long developmental and environmental influences. Genome-wide profiling of DNA methylation and gene expression was done in these three cell types from the same individuals. All cell types had distinct, statistically significant schizophrenia-associated differences in DNA methylation and linked gene expression, with Gene Ontology analysis showing that the differentially affected genes clustered in networks associated with cell growth, proliferation, and movement, functions known to be affected in schizophrenia patient-derived cells. Only five gene loci were differentially methylated in all three cell types. Understanding the role of epigenetics in cell function in the brain in schizophrenia is likely to be complicated by similar cell type differences in intrinsic and environmentally induced epigenetic regulation.

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