DNA Methylation Profiles of GAD1 in Human Cerebral Organoids of Autism Indicate Disrupted Epigenetic Regulation during Early Development

Georgina Pearson, Chenchen Song, Sonja Hohmann, Tatyana Prokhorova, Tanja Maria Sheldrick-Michel, Thomas Knöpfel

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Abstract

DNA methylation profiling has become a promising approach towards identifying biomarkers of neuropsychiatric disorders including autism spectrum disorder (ASD). Epigenetic markers capture genetic risk factors and diverse exogenous and endogenous factors, including environmental risk factors and complex disease pathologies. We analysed the differential methylation profile of a regulatory region of the GAD1 gene using cerebral organoids generated from induced pluripotent stem cells (iPSCs) from adults with a diagnosis of ASD and from age- and gender-matched healthy individuals. Both groups showed high levels of methylation across the majority of CpG sites within the profiled GAD1 region of interest. The ASD group exhibited a higher number of unique DNA methylation patterns compared to controls and an increased CpG-wise variance. We detected six differentially methylated CpG sites in ASD, three of which reside within a methylation-dependent transcription factor binding site. In ASD, GAD1 is subject to differential methylation patterns that may not only influence its expression, but may also indicate variable epigenetic regulation among cells.

Original languageEnglish
Article number9188
JournalInternational Journal of Molecular Sciences
Volume23
Issue number16
Number of pages11
ISSN1661-6596
DOIs
Publication statusPublished - 16. Aug 2022

Keywords

  • autism
  • CTCF
  • DNA methylation
  • epigenetics
  • GABA
  • GAD1
  • organoids

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