To study human astrocytes in the live adult brain, we generated chimeric mice in which human glial progenitor cells (GPCs) - isolated by sorting on the basis of an A2B5+/PSA-NCAM- phenotype, and then expanded using a protocol that promoted differentiation into hGFAP and A2B5 expressing astrocytes (Fig. S1A) - were xenografted into neonatal immune-deficient mice; these matured to become adults chimeric for both mouse and human astroglia (Windrem et al., 2004; Windrem et al., 2008). (Fig.1A). The human GPCs were labeled ex vivo, prior to implantation, with VSVg-pseudotyped lentiviral-CMV-EGFP; in antecedent pilot experiments, we had determined that this vector sustained the expression of EGFP by astroglial for at least a year in vivo (Fig. 1A). The neonatally-implanted mice were sacrificed at time-points ranging from 0.5-20 months of age, and their brains assessed both histologically and electrophysiologically. Human donor cells were first identified based on their expression of human nuclear antigen (hNuclei). The hNuclei+ cells were found to distribute relatively evenly throughout the forebrain, infiltrating both hippocampus and cortex (Fig. 1B). Human astrocytes were specifically identified by their intricate EGFP+ fluorescent
