Generation of serotonin neurons from human pluripotent stem cells

Human pluripotent stem cells are efficiently differentiated to serotonin neurons, a cell type associated with various psychiatric disorders. Serotonin neurons located in the raphe nucleus of the hindbrain have crucial roles in regulating brain functions and have been implicated in various psychiatri...

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Bibliographic Details
Published in:Nature biotechnology 2016-01, Vol.34 (1), p.89-94
Main Authors: Lu, Jianfeng, Zhong, Xuefei, Liu, Huisheng, Hao, Ling, Huang, Cindy Tzu-Ling, Sherafat, Mohammad Amin, Jones, Jeffrey, Ayala, Melvin, Li, Lingjun, Zhang, Su-Chun
Format: Article
Language:English
Subjects:
13/100
14/19
14/63
631/532/1360
631/61/2320
Agriculture
Bioinformatics
Biomedical Engineering/Biotechnology
Biomedicine
Biotechnology
Brain
Cellular biology
Drug approval
Escitalopram
Humans
Hydroxylases
letter
Life Sciences
Mental disorders
Neurons
Neurons - cytology
Neurons - metabolism
Oxalates
Oxalic acid
Phenols (Class of compounds)
Physiological aspects
Pluripotent Stem Cells - cytology
Serotonin
Serotonin - metabolism
Stem cells
Time
Tryptophan
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Summary:Human pluripotent stem cells are efficiently differentiated to serotonin neurons, a cell type associated with various psychiatric disorders. Serotonin neurons located in the raphe nucleus of the hindbrain have crucial roles in regulating brain functions and have been implicated in various psychiatric disorders. Yet functional human serotonin neurons are not available for in vitro studies. Through manipulation of the WNT pathway, we demonstrate efficient differentiation of human pluripotent stem cells (hPSCs) to cells resembling central serotonin neurons, primarily those located in the rhombomeric segments 2-3 of the rostral raphe, which participate in high-order brain functions. The serotonin neurons express a series of molecules essential for serotonergic development, including tryptophan hydroxylase 2, exhibit typical electrophysiological properties and release serotonin in an activity-dependent manner. When treated with the FDA-approved drugs tramadol and escitalopram oxalate, they release or uptake serotonin in a dose- and time-dependent manner, suggesting the utility of these cells for the evaluation of drug candidates.
ISSN:1087-0156
1546-1696
DOI:10.1038/nbt.3435