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

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

doi:10.1016/j.stemcr.2021.06.006

[해외논문] Generation of caudal-type serotonin neurons and hindbrain-fate organoids from hPSCs 원문보기

Stem cell reports, v.16 no.8, 2021년, pp.1938 - 1952

Valiulahi, Parvin (Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, 25, Bongjeong-ro, Dongnam-gu, Cheonan-si 31151, Korea) , Vidyawan, Vincencius (Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, 25, Bongjeong-ro, Dongnam-gu, Cheonan-si 31151, Korea) , Puspita, Lesly (Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, 25, Bongjeong-ro, Dongnam-gu, Cheonan-si 31151, Korea) , Oh, Youjin (Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, Korea) , Juwono, Virginia Blessy (Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, 25, Bongjeong-ro, Dongnam-gu, Cheonan-si 31151, Korea) , Sittipo, Panida (Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, 25, Bongjeong-ro, Dongnam-gu, Cheonan-si 31151, Korea) , Friedlander, Gilgi (The Mantoux Bioinformatics institute of the Nancy and Stephen Grand Israel National Center for Personalized Medicine, Weizmann Institute of Science, Rehovot 7610001, Israel) , Yahalomi, Dayana (The Mantoux Bioinformatics institute of the N) , Sohn, Jong-Woo , Lee, Yun Kyung , Yoon, Jeong Kyo , Shim, Jae-won

Abstract ▼ AI-Helper

SummarySerotonin (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.Highlights•Activation of SHH and RA signaling induces 5-HT neuronal fate from hPSCs•The generated 5-HT neurons have caudal hindbrain characteristics•Hindbrain-like organoids may form from hPSCs by activation of SHH and RA signaling•5-HT neurons in monolayer and organoid culture can be used as a screening platformIn this article, Shim and colleagues show that the generation of caudal hindbrain-type 5-HT neurons as well as 5-HT-neuron-enriched hindbrain-like organoids can be achieved through the modulation of SHH and RA signaling in differentiating hPSCs. The authors further propose that these 5-HT neurons in a monolayer and organoid culture system could be utilized as a screening platform for small molecules that trigger the release of 5-HT.

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