far fewer SCZ hGPCs manifested hGFAP expression and astrocytic phenotype (controls: 6,616 ± 672.3 GFAP+ cells/mm3 in callosum, n=12; SCZ: 1,177 ± 276.6 GFAP+ callosal cells/mm3, n=19; p<0.0001 by 2-way t-test (Figure 3C). This defect in astrocytic differentiation was consistently observed in all mice (n=19) derived from the 3 SCZ patients assessed, compared to the control GPC-engrafted mice (n=12) derived from 3 normal subjects (Figure 3D), and reflected in part the lower proportion of GFAP+ astrocytes that developed among engrafted human cells in the SCZ HGPC-engrafted brains (Figure 3E). Furthermore, Sholl analysis of individual astroglial morphologies (Sholl, 1953), as imaged in 150 μm sections and reconstructed in Neurolucida (Figure 3J), revealed that astrocytes in SCZ hGPC chimeras differed significantly from their control hGPC-derived counterparts, with fewer primary processes (Figure 3F), less proximal branching (Figure 3G), longer distal fibers (Figure 3H), and less coherent domain structure (Figure 3I). Thus, SCZ hGPCs derived from multiple patients exhibited a common defect in phenotypic maturation, and hence proved deficient in astrocytic differentiation as well as myelination.
