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

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 fro...

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Detalles Bibliográficos
Autores principales: Valiulahi, Parvin, Vidyawan, Vincencius, Puspita, Lesly, Oh, Youjin, Juwono, Virginia Blessy, Sittipo, Panida, Friedlander, Gilgi, Yahalomi, Dayana, Sohn, Jong-Woo, Lee, Yun Kyung, Yoon, Jeong Kyo, Shim, Jae-won
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8365029/
https://www.ncbi.nlm.nih.gov/pubmed/34242615
http://dx.doi.org/10.1016/j.stemcr.2021.06.006
Descripción
Sumario: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.