Significance Statement
Induced pluripotent stem cells (iPSCs) offer a great opportunity to recapitulate both normal and pathologic development of brain tissues. Recently, three research teams have developed human-PSC technology and direct somatic cell reprogramming to allow induction of human serotonin (5-hydroxytryptamine; 5-HT) neurons in vitro. While preclinical studies have repeatedly shown that 5-HT suppresses 5-HT neuronal firing activity, one group has tested the effect of 5-HT on the neuronal activity of those 5-HT-like cells and found a paradoxical excitatory action of 5-HT. Here, we argue that few cautions in translational interpretations have to be taken into account. Nonetheless, using patient-derived cells for generating disease relevant cell types truly offers a new and powerful approach for investigating mechanisms playing fundamental roles in psychiatric disorders.
Disease modeling by direct reprogramming into desired cell types represents a new huge challenge. Induced pluripotent stem cells (iPSCs), cells reprogrammed from human somatic cells, offer a great opportunity to recapitulate both normal and pathologic development of brain tissues and may as well provide essential strategies toward cell-based therapy of neuropsychiatric diseases (Vadodaria et al., 2018). Successfully, in 2016, three research teams have developed human-PSC technology (Lu et al., 2016) and direct somatic cell reprogramming (Vadodaria et al., 2016a; Xu et al., 2016) to allow induction of human serotonin neurons in vitro for the first time (for review, see Vadodaria et al., 2016b).
Remarkably, Lu et al. (2016) have demonstrated the accurate timely regulation of WNT, SHH, and FGF4 signaling pathways during the serotonergic (5-HT) neuron differentiation and generated an enriched population of 5-HT neurons from human embryonic stem cells (ESCs) and iPSCs. These human …
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