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BRAIN Publication-derived

Transient Hypoxic Injury Model in Human Cerebral Organoids

Source Daviaud et al., 2019 · Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai · 10.3389/fncel.2019.00336

👤 Nicolas Daviaud, Clément Chevalier, Roland H. Friedel, Hongyan Zou ⏱ 42 days 📋 5 phases 🧫 Human ESC (H9)

Abstract

This protocol generates dorsal forebrain-specified cerebral organoids from human H9 embryonic stem cells and models transient prenatal hypoxic injury via 24-hour exposure to 3% O₂ at day 28 of differentiation. The model allows investigation of neuroprogenitor subtype vulnerability, including differential responses of outer radial glia, intermediate progenitors, and neural stem cells to hypoxic stress during early human corticogenesis.

Cell source
Human ESC (H9)
Application
Disease modeling - Prenatal hypoxic injury and neurodevelopmental disorders

Protocol overview

12 steps across 5 phases

Embryoid Body Formation and Neural Induction D0–D14
  1. 1 Plate H9 hESCs in ultra-low attachment 96-well plates
  2. 2 Initiate neural induction
Matrigel Embedding and Initial Culture D14–D18
  1. 1 Embed organoids in Matrigel droplets
  2. 2 Culture in 6 cm Petri dishes for stationary phase
Orbital Shaker Culture and Maturation D18–D28
  1. 1 Transfer organoids to orbital shaker
  2. 2 Maintain rotating culture until hypoxia induction
Transient Hypoxic Injury Induction D28–D29
  1. 1 Transfer organoids to hypoxic chamber
  2. 2 Maintain hypoxic conditions for 24 hours
  3. 3 Return organoids to normoxic conditions
Post-Hypoxia Recovery and Analysis D29–D42
  1. 1 Continue rotating culture during recovery phase
  2. 2 Perform cell labeling studies at defined timepoints
  3. 3 Collect organoids for analysis

Full SOP

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Attribution

This SOP was authored by Organthis based on the published method in Daviaud et al., 2019. The originating laboratory holds no rights in this SOP and has not endorsed it unless marked Verified.

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