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Stem Cells International
Volume 2016, Article ID 4379425, 8 pages
Review Article

Stem Cell Models to Investigate the Role of DNA Methylation Machinery in Development of Neuropsychiatric Disorders

Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawaharnagar, Hyderabad 500 078, India

Received 31 July 2015; Accepted 10 September 2015

Academic Editor: Malin Jonsson

Copyright © 2016 K. Naga Mohan. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Epigenetic mechanisms underlie differentiation of pluripotent stem cells into different lineages that contain identical genomes but express different sets of cell type-specific genes. Because of high discordance rates in monozygotic twins, epigenetic mechanisms are also implicated in development of neuropsychiatric disorders such as schizophrenia and autism. In support of this notion, increased levels of DNA methyltransferases (DNMTs), DNMT polymorphisms, and dysregulation of DNA methylation network were reported among schizophrenia patients. These results point to the importance of development of DNA methylation machinery-based models for studying the mechanism of abnormal neurogenesis due to certain DNMT alleles or dysregulated DNMTs. Achieving this goal is strongly confronted by embryonic lethality associated with altered levels of epigenetic machinery such as DNMT1 and expensive approaches in developing in vivo models. In light of literature evidence that embryonic stem cells (ESCs) are tolerant of DNMT mutations and advancement in the technology of gene targeting, it is now possible to introduce desired mutations in DNMT loci to generate suitable ESC lines that can help understand the underlying mechanisms by which abnormal levels of DNMTs or their specific mutations/alleles result in abnormal neurogenesis. In the future, these models can facilitate development of suitable drugs for treatment of neuropsychiatric disorders.