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

ABSTRACT: Serotonin (5-HT) neurons, the major components of the raphe nuclei, arise from ventral hindbrain progenitors. Based on the 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 (NPCs) and stimulation of the hindbrain 5-HT neural development. A caudalizing agent, retinoid acid (RA), 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 have also suggested 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE167278 | GEO | 2021/04/01

REPOSITORIES: GEO

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