To assess the extent to which hiPSC-astrocytes are related to human brain astrocytes in vivo, we compared expression profiles of hiPSC-derived astrocytes, NPCs, and neurons from four healthy controls, as well as primary human fetal astrocytes, with the Allen BrainSpan Atlas of the Developing Human Brain (http://www.brainspan.org) (Miller et al., 2014) using a Spearman rank correlation analysis. Heatmaps generated through a Wilcoxon's rank-sum test revealed that gene expression in hiPSC-astrocytes and primary human fetal astrocytes was highly correlated with gene expression in human fetal cortical brain tissue (8–16 weeks post conception) (Figure 2F). Unsupervised hierarchical cell-type-specific cluster analysis demonstrated that hiPSC-astrocytes closely cluster with astrocytes purified by immunopanning from human brain tissue, particularly hippocampal astrocytes, rather than oligodendrocytes, endothelial cells, myeloid cells, or neurons (Zhang et al., 2016) (Figure 3A); pathway analysis further revealed that many astrocyte-enriched genes were related to immune signaling (Figure 2G).
