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

Parvin Valiulahi, Vincencius Vidyawan, Lesly Puspita, Youjin Oh, Virginia Blessy Juwono, Panida Sittipo, Gilgi Friedlander, Dayana Yahalomi, Jong Woo Sohn, Yun Kyung Lee, Jeong Kyo Yoon, Jae won Shim

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1938-1952
Number of pages15
JournalStem Cell Reports
Volume16
Issue number8
DOIs
StatePublished - 10 Aug 2021
Externally publishedYes

Keywords

  • hindbrain
  • human pluripotent stem cells
  • neuronal development
  • organoids
  • serotonin neurons

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