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BRAIN Publication-derived

Patient-Derived Cerebral Organoid Generation for Schizophrenia Disease Modeling

Source Notaras et al., 2022 · Center for Neurogenetics, Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, Cornell University · 10.1038/s41380-021-01316-6

👤 Michael Notaras, Aiman Lodhi, Friederike Dündar, Paul Collier, Nicole M. Sayles, Hagen Tilgner, David Greening, Dilek Colak ⏱ 42 days 📋 5 phases 🧫 Patient-Derived iPSC (Schizophrenia)

Abstract

This protocol generates 3D patient-derived cerebral organoids from idiopathic schizophrenia and healthy control iPSC lines to model cell-specific neuropathology during early brain development. The organoids recapitulate ventricular zone disruption, altered neurogenesis, and molecular signatures of schizophrenia, enabling mechanistic study of developmental disease mechanisms.

Cell source
Patient-Derived iPSC (Schizophrenia)
Application
Disease modeling of early neurodevelopmental pathology in Schizophrenia

Protocol overview

13 steps across 5 phases

iPSC Maintenance and Quality Control Ongoing (before organoid generation)
  1. 1 Maintain iPSC lines on Vitronectin-coated plates
  2. 2 Screen control lines for mental health history
Embryoid Body Formation Days 0–7
  1. 1 Dissociate iPSC colonies
  2. 2 Culture embryoid bodies in ultra-low attachment plates
  3. 3 Monitor embryoid body quality
Neural Fate Specification and Neuroepithelium Formation Days 7–14
  1. 1 Transfer embryoid bodies to neural induction plates
  2. 2 Monitor for neuroepithelium formation
Matrigel Embedding and 3D Expansion Days 14–21
  1. 1 Embed organoids in Matrigel droplets
  2. 2 Culture organoids without agitation
  3. 3 Initiate orbital shaker culture
Extended Maturation and Maintenance Days 21 onwards (typically to day 35–42 for core phenotyping)
  1. 1 Continue orbital shaker culture with media changes
  2. 2 Rolling quality control assessment
  3. 3 Harvest organoids for experimentation

Full SOP

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Attribution

This SOP was authored by Organthis based on the published method in Notaras et al., 2022. The originating laboratory holds no rights in this SOP and has not endorsed it unless marked Verified.

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