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Chunk #12 — Human glia maintain uniquely hominid features in chimeras

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Modeling cognition and disease using human glial chimeric mice.
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On the basis of these observations, we asked if the greater structural complexity of human astrocytes relative to those of rodents might be accompanied by functional differences. In particular, we asked whether human glial chimeric mouse brains, with their substantial colonization by human astroglia and their progenitors, might manifest functional distinctions from wild-type mice, and if so whether these functional differences might reflect aspects of human cognitive evolution (Han et al. 2013). This possibility was anticipated by the observation that human astrocytes propagate Ca2+ waves significantly more rapidly than rodents (Oberheim et al. 2009). To define the human-selective contributions of astrocytic complexity to network function, we therefore assessed the behavior of human glial chimeras to both matched unengrafted and allografted mice. To that end, hGPCs, pre-biased in vitro to astrocytic phenotype, were transplanted into neonatal immunodeficient mice, thereby establishing human glial chimeras with especially large complements of human astrocytes as well as GPCs. By 7–10 months of age, the majority of all forebrain OPCs and astrocytes in these mice were typically of human origin (Figure 2). The engrafted human glia