Disorganized migration of proliferating cells and depletion of cortical neurons in schizophrenia iPSC cerebral organoidsOrganoids were coimmunostained for Ki67 (red) and Pan-Neu (green). Nuclei were stained with DAPI (blue). a 2-week organoids—images show representative sections of organoids, control (iPSC line BJ1) and schizophrenia (iPSC line 1835). In schizophrenia organoids, note the dispersion of proliferating (Ki67+) cells outside the VZ into IZ and CZ, fewer mature Pan-Neu+ neurons in CZ, and the appearance of Pan Neu+ neurons in the IZ. b 5-week iPSC organoids: control (line 2937) and schizophrenia (line 2038)—representative images of control and schizophrenia organoids. In schizophrenia organoids, note dispersion of Ki67+ cells into CZ, reduced density of Pan Neu+ neurites in basal CZ and the presence of Pan Neu+ cells with neurites in the IZ. 3D rotational confocal images of control (line 3651) and schizophrenia (line 1835) organoids are shown in Video 1a and b. Pan-Neu immunofluorescence intensity was measured in multiple randomly selected ROI (1 × 102 μm2 in basal cortex (*) and in IZ (**)). c 5-week organoids—Pan-Neu immunofluorescence intensity was measured in several ROIs (# shown on y-axis) of multiple organoids from three control and three schizophrenia patients. Note, significantly reduced Pan-Neu fluorescence intensity in basal cortex of the schizophrenia organoids and the lack of significant changes in the IZ. d Distribution of Pan-Neu intensity numbers in analyzed ROIs. Note the significant separation of the basal cortex plots in control and schizophrenia organoids and the lack of separation of the IZ plots
