The characterization of gene expression during mouse neural stem cell differentiation in vitro.

Neural stem cells (NSCs) are tissue-specific, multipotent stem cells that can differentiate into three cell lineages in the central nervous system: neurons, astrocytes and oligodendrocytes. The therapeutic potential of NSCs has fueled attempts to characterize the expression of genes that regulate their fate. In this study, NSCs from embryonic day 15 (E15) mouse embryos were differentiated for 1 (DF-1) or 2 (DF-2) days, and the gene expression patterns in the NSCs and in the DF-1 and DF-2 cells were measured by microarray and real-time RT-PCR. Among the analyzed genes, 1898 genes were up-regulated in the DF-1 and DF-2 cells relative to the NSCs, whereas 1642 genes were down-regulated. The up-regulated genes included Gfap, Smad6, Fst, Tgfb2 and Cdkn2. The down-regulated genes included Ccnb1, Ccnd1 and Ccnd2. We identified gene networks that were associated with BMP and TGF-beta2 signaling pathways using Ingenuity Pathway Analysis. Our results suggest that the differentiation of E15 NSCs into astrocytes is based on a combinatorial network of various signaling pathways, including cell cycle, BMP and TGF-beta2 signaling.