The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Single-cell RNAseq reveals seven classes of colonic sensory neuron
Open accessAbstract
Objective: Integration of nutritional, microbial and inflammatory events along the gut-brain axis can alter bowel physiology and organism behaviour. Colonic sensory neurons activate reflex pathways and give rise to conscious sensation, but the diversity and division of function within these neurons is poorly understood. The identification of signalling pathways contributing to visceral sensation is constrained by a paucity of molecular markers. Here we address this by comprehensive transcriptomic profiling and unsupervised clustering of individual mouse colonic sensory neurons. Design: Unbiased single-cell RNA-sequencing was performed on retrogradely traced mouse colonic sensory neurons isolated from both thoracolumbar (TL) and lumbosacral (LS) dorsal root ganglia associated with lumbar splanchnic and pelvic spinal pathways, respectively. Identified neuronal subtypes were validated by single-cell qRT-PCR, immunohistochemistry (IHC) and Ca 2+ -imaging. Results: Transcriptomic profiling and unsupervised clustering of 314 colonic sensory neurons revealed seven neuronal subtypes. Of these, five neuronal subtypes accounted for 99% of TL neurons, with LS neurons almost exclusively populating the remaining two subtypes. We identify and classify neurons based on novel subtype-specific marker genes using single-cell qRT-PCR and IHC to validate subtypes derived from RNA-sequencing. Lastly, functional Ca 2+ -imaging was conducted on colonic sensory neurons to demonstrate subtype-selective differential agonist activation. Conclusions: We identify seven subtypes of colonic sensory neurons using unbiased single-cell RNA-sequencing and confirm translation of patterning to protein expression, describing sensory diversity encompassing all modalities of colonic neuronal sensitivity. These results provide a pathway to molecular interrogation of colonic sensory innervation in health and disease, together with identifying novel targets for drug development.
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Unbiased classification of sensory neuron types by large-scale single-cell RNA sequencing
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Self-citationEnterochromaffin cells are gut chemosensors that couple to sensory neural pathways
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Role of the endocannabinoid system in the regulation of intestinal homeostasis
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Neuronal diversity in the somatosensory system: bridging the gap between cell type and function
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Estacion, M., Liu, S., Cheng, X., Dib-Hajj, S., & Waxman, S. G. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1138556 · Cited by 11
Metadata
- Authors
- Hockley, J. R. F., Taylor, T. S., Callejo, G., Wilbrey, A. L., Gutteridge, A., Bach, K., Winchester, W. J., Bulmer, D. C., McMurray, G., & Smith, E. S. J.
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2018-02-26
- Volume
- 68
- Issue
- 4
- Pages
- 633-644
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2788398310
- Cited by
- 256
- References
- 10
- FWCI
- 8.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
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