Regardless of its molecular basis, the domination of the host brains by human GPCs leads to the slow but inexorable glial humanization of these brains, as mature astrocytes undergo presumably normal turnover in adulthood, with astrocytic replacement from now-humanized resident progenitor pools. This process results in the substantial astrocytic humanization of these rodent brains, first by fibrous astrocytes of the white matter, and then by protoplasmic astroglia of both cortical and subcortical gray matter (Windrem et al. 2008) (Figure 2). In both shiverer and myelin wild-type hosts, the proportion of human astrocytes thus increases monotonically as a function of time, and is matched by a corresponding decrease in the proportion of mouse astrocytes. Over time, these brains thus become chimeric for human astrocytes, as well as for human glial progenitors, and in shiverer mice, this process includes replacement of host oligodendrocytes by their human counterparts as well. As a result, in one-year old shiverer mice neonatally engrafted with human GPCs, essentially all resident glial progenitor cells, all oligodendrocytes, and large proportions of all astrocytes are of human origin (Figure 2).
