Generation of caudal-type serotonin neurons and hindbrain-fate organoids from hPSCs

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Serotonin (5-HT) neurons, the major components of the raphe nuclei, arise from ventral hindbrain progenitors. Based on anatomical location and axonal projection, 5-HT neurons are coarsely divided into rostral and caudal groups. Here, we propose a novel strategy to generate hindbrain 5-HT neurons from human pluripotent stem cells (hPSCs), which involves the formation of ventral-type neural progenitor cells and stimulation of the hindbrain 5-HT neural development. A caudalizing agent, retinoid acid, was used to direct the cells into the hindbrain cell fate. Approximately 30%-40% of hPSCs successfully developed into 5-HT-expressing neurons using our protocol, with the majority acquiring a caudal rhombomere identity (r5-8). We further modified our monolayer differentiation system to generate 5-HT neuron-enriched hindbrain-like organoids. We also suggest downstream applications of our 5-HT monolayer and organoid cultures to study neuronal response to gut microbiota. Our methodology could become a powerful tool for future studies related to 5-HT neurotransmission.
Publisher
CELL PRESS
Issue Date
2021-08
Language
English
Article Type
Article
Citation

STEM CELL REPORTS, v.16, no.8, pp.1938 - 1952

ISSN
2213-6711
DOI
10.1016/j.stemcr.2021.06.006
URI
http://hdl.handle.net/10203/287490
Appears in Collection
BS-Journal Papers(저널논문)
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