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Chunk #12 — RESULTS — SCZ hGPCs showed cell-autonomous misexpression of differentiation-associated genes

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Human iPSC Glial Mouse Chimeras Reveal Glial Contributions to Schizophrenia.
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To better define the molecular basis for the apparent impediment to terminal glial differentiation in SCZ GPC-engrafted mice, and to define which aspects of that deficit might be cell-autonomous, we next used RNA-seq analysis to identify the differentially expressed genes of SCZ iPSC-derived GPCs, relative to those of control-derived glia. We used sequencing data to reconstruct the transcriptional patterns of hGPCs derived from 4 different SCZ and 3 control patients. hGPCs were derived at time points ranging from 154 to 242 days in vitro, and sorted for hGPCs using CD140a-targeted FACS. Using a 5% FDR and a fold-change threshold of 2, we identified a total of 118 mRNAs that were differentially expressed by CD140a-sorted SCZ hGPCs relative to their control iPSC hGPCs (Figures 4A–B). Among those genes most differentially expressed by CD140a-sorted SCZ hGPCs were a host of glial differentiation-associated genes, in particular those associated with early oligodendroglial and astroglial lineage progression, which were uniformly down-regulated in the SCZ hGPCs relative to their normal controls (Figures 4C and 4F). These included a coherent set of the key GPC lineage transcription