The importance of the gut in regulating the brain–body immune axis is becoming increasingly evident. Interestingly, the brain and gut share many common signaling molecules, with serotonin being one of the most notable. In fact, the gut is the primary source of serotonin in the body. However, studying serotonin dynamics in a human-specific context remains a challenge. Human stem cell-derived models provide a promising avenue for studying signal transmission in well-controlled, in vitro environments. In this study, we report the first fast-scan cyclic voltammetry (FSCV) measurements of serotonin signaling in a newly developed enterochromaffin cell (ECC)-enriched gut organoid model. First, we characterize the stem cell-derived gut organoids and confirm they are enriched with ECCs, the key cell type responsible for producing and releasing serotonin in the gut. We then optimize an in vitro buffer that maintains cell viability while supporting FSCV measurements. Using this system, we detect spontaneous release events, which increase in frequency and amplitude following stimulation with forskolin (FSK) and 3-isobutyl-1-methylxanthine (IBMX). Finally, we confirm the identity of the signal as serotonin using a selective serotonin reuptake inhibitor (SSRI), which significantly delayed the reuptake profile. Our study introduces the first real-time measurement of serotonin signaling in a human-derived gut model. We believe this system will be essential for future research on serotonin’s role in the gut and for potential novel drug target identification.

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Identification of an LGR5 as a marker for a tripotent stem/progenitor cell of the human fetal pancreas. Organoids derived from single LGR5+ cells are capable of long-term expansion in vitro and genera...

This study identifies parallel gut–brain pathways that fine-tune feeding. Distinct brainstem neurons and visceral afferents either sense esophageal stretch to regulate eating speed or detect gut nutri...

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Human brain organoids are powerful in vitro models for brain development and disease. However, their variability can complicate use in biomedical research and drug discovery. Both the specific protoco...

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Stem cells perceive and respond to biochemical and physical signals to maintain homeostasis. Yet, it remains unclear how stem cells sense mechanical signals from their niche in vivo. In this work, we ...

To elucidate aging-associated cellular population dynamics, we present PanSci, a single-cell transcriptome atlas profiling over 20 million cells from 623 mouse tissues across different life stages, se...

The brain senses changes to the internal state of the body, eliciting responses that maintain homeostasis. Alhadeff and Yapici provide an overview of this process, termed interoception, with a particu...