To further explore the molecular mechanisms underpinning the premature neuronal differentiation, we measured the protein level of doublecortin (DCX), a marker of immature newborn neurons [29]. We found that DCX level was markedly higher in AD-NPCs at day 28 of neuronal differentiation (Figure 6c and 6d) than that in N-NPCs. Furthermore, we identified β-catenin as one of the up-stream transcription factors of the differentially expressed genes (Supplementary Figure 4a). Western blot analyses revealed that its protein level decreased significantly in AD-NPCs at day 28 of neuronal differentiation (Figure 6e and 6f), suggesting that β-catenin might act as a repressor of neuronal differentiation. In addition, Notch signaling is known to play important roles in the maintenance of neural stem cells during development through controlling the transcription of its targets [30]. Interestingly, we found that the protein level of Notch intracellular domain (NICD), an intracellular effector of Notch signaling and a catalytic product of PSEN1 [31], was significantly decreased in AD-NPCs on day 28 of differentiation (Supplementary Figure 4b). In line with this finding, the transcript levels of Notch direct targets (HES1
