In the course of these studies, we noticed two unexpected outcomes. First, that hGPCs mature in a highly context-dependent fashion, such that those donor cells that engraft presumptive white matter develop as myelinogenic oligodendrocytes and fibrous astrocytes, while those cells invading cortical and subcortical gray matter that differentiate do so as astrocytes(Windrem et al. 2004). These observations recall earlier studies of context-dependent differentiation by murine neural stem cells (NSCs) transplanted into shiverers, which typically differentiated as oligodendroglia in the white matter, and as astrocytes in the gray matter (Mitome et al. 2001; Yandava et al. 1999). Just as in those studies, the phenotypic malleability of hGPCs by the local environment is profound, so much so that the distribution as well as the differentiation of hGPCs differs depending upon whether the cells are transplanted into normally-myelinated or congenitally-hypomyelinated recipients: in myelin wild-types, transplanted hGPCs infiltrate in a relatively uniform fashion in both the gray and white matter, ultimately differentiating as astrocytes or remaining as resident glial progenitors. In contrast, hGPCs transplanted into shiverer mice first preferentially expand in the callosal and capsular white matter, giving rise therein to new oligodendrocytes as well as astrocytes and daughter hGPCs (Figure 2).
