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Progress in iPSC-Based Modeling of Psychiatric Disorders.
Hoffmann, Anke; Ziller, Michael; Spengler, Dietmar.
Affiliation
  • Hoffmann A; Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, 80804 Munich, Germany. hoffmann@psych.mpg.de.
  • Ziller M; Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, 80804 Munich, Germany. michael_ziller@psych.mpg.de.
  • Spengler D; Department of Translational Research in Psychiatry, Max-Planck Institute of Psychiatry, 80804 Munich, Germany. spengler@psych.mpg.de.
Int J Mol Sci ; 20(19)2019 Oct 02.
Article in En | MEDLINE | ID: mdl-31581684
Progress in iPSC-based cellular systems provides new insights into human brain development and early neurodevelopmental deviations in psychiatric disorders. Among these, studies on schizophrenia (SCZ) take a prominent role owing to its high heritability and multifarious evidence that it evolves from a genetically induced vulnerability in brain development. Recent iPSC studies on patients with SCZ indicate that functional impairments of neural progenitor cells (NPCs) in monolayer culture extend to brain organoids by disrupting neocorticogenesis in an in vitro model. In addition, the formation of hippocampal circuit-like structures in vitro is impaired in patients with SCZ as is the case for glia development. Intriguingly, chimeric-mice experiments show altered oligodendrocyte and astrocyte development in vivo that highlights the importance of cell-cell interactions in the pathogenesis of early-onset SCZ. Likewise, cortical imbalances in excitatory-inhibitory signaling may result from a cell-autonomous defect in cortical interneuron (cIN) development. Overall, these findings indicate that genetic risk in SCZ impacts neocorticogenesis, hippocampal circuit formation, and the development of distinct glial and neuronal subtypes. In light of this remarkable progress, we discuss current limitations and further steps necessary to harvest the full potential of iPSC-based investigations on psychiatric disorders.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Induced Pluripotent Stem Cells / Mental Disorders / Models, Biological Type of study: Diagnostic_studies / Prognostic_studies Limits: Animals / Humans Language: En Journal: Int J Mol Sci Year: 2019 Document type: Article Affiliation country: Germany Country of publication: Switzerland

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Induced Pluripotent Stem Cells / Mental Disorders / Models, Biological Type of study: Diagnostic_studies / Prognostic_studies Limits: Animals / Humans Language: En Journal: Int J Mol Sci Year: 2019 Document type: Article Affiliation country: Germany Country of publication: Switzerland