GSE134216
Cell-to-cell adhesion and neurogenesis in human cortical development: a study comparing 2D monolayers with 3D organoid cultures
Organoids (ORG) are increasingly used as models of cerebral cortical development. Here we compared transcriptome and cellular phenotypes between ORG and monolayers (MON) generated in parallel from three biologically distinct iPSC lines. Multiple read-outs revealed increased proliferation in MON, which was caused by increased integrin signaling. MON also exhibited altered radial glia polarity, global suppression of Notch signaling and impaired generation of intermediate progenitors (INP), outer radial glia (oRG) and cortical neurons, which  were all partially reversed by reaggregation of dissociated cells into organoids. Network analyses revealed co-clustering of cell adhesion, Notch- related transcripts their transcriptional regulators in a module strongly downregulated in MON. The data suggest that cortical ORG, with respect to MON, initiates more efficient Notch signaling in ventricular radial glia owing to preserved cell adhesion, resulting in subsequent generation of INP and oRG, in a sequence that better recapitulates the evolution of the cortical ontogenetic process. Overall design: Examination of 3 cell lines at 3 differentiation time points