Your browser doesn't support javascript.
loading
Stem Cell Models for Context-Specific Modeling in Psychiatric Disorders.
Seah, Carina; Huckins, Laura M; Brennand, Kristen J.
Affiliation
  • Seah C; Pamela 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.
  • Huckins LM; Pamela 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; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York; Seaver Autism Center for Research and Treatment, Icahn School of Medicine at Mount Sinai, New York; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. Electronic address: laura.huckins@yale.edu.
  • Brennand KJ; Pamela 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; Department of Psychiatry, 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; Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut. Electronic address: kriste
Biol Psychiatry ; 93(7): 642-650, 2023 04 01.
Article in En | MEDLINE | ID: mdl-36658083
Genome-wide association studies reveal the complex polygenic architecture underlying psychiatric disorder risk, but there is an unmet need to validate causal variants, resolve their target genes(s), and explore their functional impacts on disorder-related mechanisms. Disorder-associated loci regulate transcription of target genes in a cell type- and context-specific manner, which can be measured through expression quantitative trait loci. In this review, we discuss methods and insights from context-specific modeling of genetically and environmentally regulated expression. Human induced pluripotent stem cell-derived cell type and organoid models have uncovered context-specific psychiatric disorder associations by investigating tissue-, cell type-, sex-, age-, and stressor-specific genetic regulation of expression. Techniques such as massively parallel reporter assays and pooled CRISPR (clustered regularly interspaced short palindromic repeats) screens make it possible to functionally fine-map genome-wide association study loci and validate their target genes at scale. Integration of disorder-associated contexts with these patient-specific human induced pluripotent stem cell models makes it possible to uncover gene by environment interactions that mediate disorder risk, which will ultimately improve our ability to diagnose and treat psychiatric disorders.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Induced Pluripotent Stem Cells / Mental Disorders Type of study: Diagnostic_studies / Prognostic_studies Limits: Humans Language: En Journal: Biol Psychiatry Year: 2023 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Induced Pluripotent Stem Cells / Mental Disorders Type of study: Diagnostic_studies / Prognostic_studies Limits: Humans Language: En Journal: Biol Psychiatry Year: 2023 Document type: Article Country of publication: United States