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Updated: Jun 30, 2026

Generation of iPSC-derived Human Brain Organoids to Model Early Neurodevelopmental Disorders
Published on: April 14, 2017
Human cortical organoids recapitulate inter-individual variability in infant brain-growth trajectories
Madison R Glass1, Nana Matoba1, Alvaro A Beltran1
1Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Human cortical organoids (hCOs) derived from induced pluripotent stem cells (iPSCs) model individual brain development. These organoids reflect infant cortical growth rates and are linked to neurodevelopmental disorder genes.
Area of Science:
- Neuroscience
- Developmental Biology
- Stem Cell Biology
Background:
- Induced pluripotent stem cell (iPSC)-derived human cortical organoids (hCOs) offer a platform to study neurodevelopment in vitro.
- The extent to which hCO phenotypes mirror in vivo brain growth in individuals is not fully understood.
Purpose of the Study:
- To assess the recapitulation of individual brain growth patterns in hCOs.
- To investigate the relationship between hCO characteristics and infant cortical development.
Main Methods:
- Generated up to 3 iPSC clones from 18 participants in the Infant Brain Imaging Study.
- Performed longitudinal brain imaging on participants during infancy.
- Analyzed hCO morphology, cell types, cross-sectional area, hem/choroid plexus production, and gene expression.
Main Results:
- Consistent hCO morphology and cell types were observed across clones from the same individual.
- hCO cross-sectional area and hem/choroid plexus production correlated with in vivo cortical growth rates.
- Cell-cycle gene expression in early progenitors linked to 6-12 month cortical growth rates and was enriched for microcephaly and neurodevelopmental disorder genes.
Conclusions:
- hCOs capture inter-individual variations in cortical cell types.
- These variations influence infant cortical surface area expansion.
- hCOs serve as a valuable model for studying genetic influences on neurodevelopment.
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