Human cortical organoids recapitulate inter-individual variability in infant brain-growth trajectories.

Abstract

Induced pluripotent stem cell (iPSC)-derived human cortical organoids (hCOs) model neurogenesis on an individual's genetic background. The degree to which hCO phenotypes recapitulate the brain growth of the participants from whom they were derived is not well established. We generated up to 3 iPSC clones from each of 18 participants in the Infant Brain Imaging Study, who underwent longitudinal brain imaging during infancy. We identified consistent hCO morphology and cortical cell types across clones from the same participant. hCO cross-sectional area and production of hem/choroid plexus were associated with in vivo cortical growth rates. Cell-cycle-associated gene expression in early progenitors at the crux of fate-decision trajectories was correlated with cortical growth rates from 6 to 12 months of age and was enriched for microcephaly and neurodevelopmental disorder genes. Our data suggest the hCOs capture inter-individual variation in cortical cell types that influences infant cortical surface area expansion.