Schizophrenia-derived hGPCs exhibit aberrant dispersal and relative hypomyelinationHuman iPSC GPC chimeras were established by neonatal hGPC injection into shiverer hosts and sacrificed at 19 weeks. GPCs derived from a control subject (A) dispersed primarily in the major white matter tracts, whereas (B) SCZ-derived GPCs (15 yo male) showed less white matter residence and more rapid cortical infilitration. C–D, Sagittal sections reveal that callosal myelination by SCZ GPCs (D) was less dense than that by control hGPCs (C). E–F, Higher power images from chimeric mice engrafted with hGPCs from 4 control patients (E) vs. chimeric mice engrafted with hGPCs from 4 different SCZ patients (F). G, MBP luminance confirmed the greater callosal myelination of CTRL GPC-engrafted vs. SCZ GPC-engrafted mice at 19 weeks (means of 4 different SCZ and CTRL patients each, n>3 mice/patient) (p=0.0002, t-test). H, Absolute donor cell densities were lower in SCZ than control hGPC-engrafted corpus callosum (p<0.0001, t-test), as were the densities of olig2+ hGPCs and oligodendroglia (I) (p=0.0064, t-test) and transferrin (TFN)+ oligodendroglia (J) (p<0.0001, t-test).See also Figure S2.
