These data suggest a significant contribution of cell-autonomous glial pathology to the genesis and development of juvenile-onset schizophrenia. In these human glial chimeric mice, schizophrenia-derived iPSC hGPCs exhibited aberrant migration with deficient engraftment in the central white matter, relative to age-analogous and gender-matched control iPSC hGPCs. Although a fraction of those SCZ hGPCs that did remain within the white matter differentiated as normal myelinogenic oligodendroglia, the premature cortical influx and hence lower density of donor-derived cells in the white matter of SCZ hGPC-engrafted mice resulted in the latter’s overt hypomyelination, relative to mice engrafted with control GPCs. Thus, SCZ hGPCs appeared to traverse rather than home in to the nascent white matter, resulting in sparse hGPC colonization and hence deficient forebrain myelination. The aberrant dispersal pattern of SCZ hGPCs suggests that SCZ GPCs may not recognize developmental stop signals that permit progenitors to dwell and expand within the presumptive white matter before colonizing the cortical mantle, and may instead be biased towards rapid entry into the cortical gray matter. These observations in human SCZ glial chimeric mice are especially intriguing
