Proceedings
The Effect of Notch Signaling In Hindbrain Serotonin Neurons Differentiation From Human Pluripotent Stem Cells
Serotonin (5-HT) neurons are currently of research interest since these neurons have a crucial role in regulating human homeostasis and psychological states. These neurons are generated from the hindbrain raphe nuclei and are classified into rostral (r1-r3) and caudal (r5-r8) groups. While rostral groups have been successfully developed, only a few functional caudal 5-HT neurons are available in vitro, limiting their potential use for downstream applications. On the other hand, activation of the notch signaling pathway is known to prevent neuronal differentiation; therefore, blocking this pathway using ɣ-secretase inhibitor (DAPT) is expected to overcome the issues. In this study, DAPT molecules were administered at various time points during the 5-HT neuronal differentiation in vitro. Apparently, DAPT molecules could only accelerate neuronal maturation but did not seem potent in 5-HT neuronal patterning. The particular reason for this might be due to the inhibition of notch signaling that triggers premature differentiation and prevents the neuronal cells from properly maturing into 5-HT neurons. In addition, the effects of DAPT treatment during brain development were also assessed based on organoid 3D cultures. Evidently, the addition of DAPT molecules led to an abnormal cerebral organoid differentiation, indicating the importance of notch signaling pathways during cerebral organoid development.
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