Transcriptomic mapping of the 5-HT receptor landscape

• Published in: Patterns (New York, N.Y.) Vol. 5; no. 10; p. 101048
• Main Authors: De Filippo, Roberto, Schmitz, Dietmar
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 11-10-2024; Elsevier
• Subjects: 5-HT; 5-HT receptors; MERFISH; scRNA-seq; serotonin; transcriptomics; MERFISH; transcriptomics; serotonin; scRNA-seq; 5-HT; 5-HT receptors
• ISSN: 2666-3899; 2666-3899
• DOI: 10.1016/j.patter.2024.101048

Serotonin (5-HT) is crucial for regulating brain functions such as mood, sleep, and cognition. This study presents a comprehensive transcriptomic analysis of 5-HT receptors (Htrs) across ≈4 million cells in the adult mouse brain using single-cell RNA sequencing (scRNA-seq) data from the Allen Institute. We observed differential transcription patterns of all 14 Htr subtypes, revealing diverse prevalence and distribution across cell classes. Remarkably, we found that 65.84% of cells transcribe RNA of at least one Htr, with frequent co-transcription of multiple Htrs, underscoring the complexity of the 5-HT system even at the single-cell dimension. Leveraging a multiplexed error-robust fluorescence in situ hybridization (MERFISH) dataset provided by Harvard University of ≈10 million cells, we analyzed the spatial distribution of each Htr, confirming previous findings and uncovering novel transcription patterns. To aid in exploring Htr transcription, we provide an online interactive visualizer.
[Display omitted]
•Analysis of 5-HT-receptor single-cell mouse whole-brain transcriptomic atlases•Extensive co-transcription points at considerable complexity at the single-cell level•Interactive visualizer for custom exploration at different levels of granularity
Serotonin (5-HT) receptors are neurotransmitter receptor proteins with relevant roles in mood regulation, cognition, and sleep. Understanding their distribution and transcription complexity is crucial for studying overall brain function. This study leverages state-of-the-art single-cell RNA sequencing and spatial transcriptomics data to map 5-HT receptor subtypes across millions of cells in the mouse brain. The findings in this study highlight the extensive presence of these receptors, often co-transcribed within the same cell, pointing to the single-cell-level complexity of the serotonergic system, the neural system in charge of the release of neurotransmitters essential for physiological and behavioral processes such as appetite and mood regulation, cognition, and sleep. Here, we provide an interactive visualization tool to explore these data. This work sets the stage for more targeted investigations into the functional implications of 5-HT receptor distribution, with potential impacts on understanding and treating psychiatric and neurological disorders.
Serotonin (5-HT) plays a critical role in numerous physiological and pathological processes. De Filippo and Schmitz analyzed two advanced transcriptomic atlases to map the transcription patterns of 5-HT receptors across millions of cells. Their findings reveal diverse transcription patterns of various 5-HT receptor genes. An interactive online tool is provided for custom data exploration, allowing quick, in-depth analysis across multiple grouping variables and facilitating a deeper understanding of 5-HT receptors and their implications for brain function and disorders.