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Embryonic and induced pluripotent stem cells are excellent models for disease research because of their ability to self-renew and differentiate into most cell types. Somatic cells from a patient are isolated and reprogrammed into induced pluripotent stem cells or iPSCs. These iPSCs are later differentiated into the desired cell type, which mirrors the diseased cell of the patient. In this way, disease models have been created for investigating diseases such as Down syndrome, type I diabetes,...
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Related Experiment Video

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Stem Cell Models for Context-Specific Modeling in Psychiatric Disorders.

Carina Seah1, Laura M Huckins2, Kristen J Brennand3

  • 1Pamela Sklar Division of Psychiatric Genomics, Icahn School of Medicine at Mount Sinai, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York; Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York.

Biological Psychiatry
|January 19, 2023
PubMed
Summary
This summary is machine-generated.

This review explores how cell-specific gene expression models, using human stem cells, can identify psychiatric disorder risk genes. These methods help understand genetic and environmental influences on complex brain disorders.

Keywords:
CRISPRExpression quantitative trait loci (eQTL)Genome-wide association studies (GWASs)Human induced pluripotent stem cellsMassively parallel reporter assays (MPRAs)

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Psychiatric disorders have a complex genetic basis, requiring validation of causal variants and their functional impact.
  • Understanding cell-type and context-specific gene regulation is crucial for psychiatric disorder research.

Purpose of the Study:

  • To review methods for context-specific modeling of gene expression in psychiatric disorders.
  • To highlight insights from human induced pluripotent stem cell (hiPSC) models and functional genomics techniques.

Main Methods:

  • Expression quantitative trait loci (eQTL) analysis for cell-specific regulation.
  • Human induced pluripotent stem cell-derived cell types and organoids.
  • Massively parallel reporter assays and pooled CRISPR screens for gene validation.
  • Integration of disorder-associated contexts with hiPSC models.

Main Results:

  • Context-specific modeling reveals psychiatric disorder associations across various tissues, cell types, and conditions.
  • Functional fine-mapping and gene validation at scale are enabled by reporter assays and CRISPR screens.
  • Gene by environment interactions mediating disorder risk can be uncovered using hiPSC models.

Conclusions:

  • Context-specific modeling using hiPSC-derived systems is a powerful approach to dissecting psychiatric disorder risk.
  • These integrated methods advance the understanding of genetic and environmental contributions to psychiatric disorders.
  • This research holds promise for improved diagnosis and treatment strategies for psychiatric disorders.