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Chunk #30 — DISCUSSION

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Human iPSC Glial Mouse Chimeras Reveal Glial Contributions to Schizophrenia.
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Schizophrenia is genetically heterogeneous, so that anatomic and behavioral pathology may vary significantly among animals chimerized with GPCs derived from different patients. It is thus critical that the results obtained from chimeras established with control hiPSC GPCs be stable across both distinct lines of donor cells, and among recipient mice. The chimeric brains established from the hGPCs of 3 different SCZ patients were thus compared anatomically to those established from GPCs derived from 3 control patients. None of the controls manifested the white matter-avoidant dispersal pattern of the SCZ hGPC chimeras. Similarly, we had never noted this pattern of SCZ hGPC avoidance of the white matter in any of several hundred human glial chimeras engrafted in other studies with either fetal tissue-derived (Windrem et al., 2008; Windrem et al., 2014) or normal iPSC-derived (Wang et al., 2013) hGPCs.