To explore the molecular basis of premature neuronal differentiation in AD-NPCs, we compared the whole genome transcript profiling between four AD-NPCs lines and three normal control NPCs lines at day 32 of differentiation. Data analysis uncovered 430 up-regulated genes (at a change level ≥ 2 folds; p < 0.05) and 266 down-regulated genes (at a change level ≤ 0.5-fold; p < 0.05) (Figure 6a). Gene ontology (GO) analyses showed that up-regulated genes encode molecules associated with neuron development, neuron projection, neuron maturation, cell morphogenesis involved in neuron differentiation, which were in accordance with the abnormally enhanced neuronal differentiation observed in differentiated AD-NPCs. Down-regulated genes mainly encode the molecules involved in the regulation of cell cycle, nuclear division and condensed chromosomes, which might explain the reduction of cell proliferation and induction of cell apoptosis in differentiated AD-NPCs (Figure 6b). Among the up-regulated genes, there were previously reported AD associated genes, such as HTR2A, ANK3, BDNF, IL18, LRP8, MAPT, PPARα, SLC18A3 and VDR (david.abcc.ncifcrf.gov). In addition, we screened for the up-stream transcription factors for the differentially expressed genes, which might control aberrant
