Stratification of enterochromaffin cells by single-cell expression analysis.
Yan Song, Linda J Fothergill, Kari S Lee, Brandon Y Liu, Ada Koo, Mark Perelis, Shanti Diwakarla, Brid Callaghan, Jie Huang, Jill Wykosky, John B Furness, Gene W Yeo
eLife · 2025 · Vol. 12
Abstract
Dynamic interactions between gut mucosal cells and the external environment are essential to maintain gut homeostasis. Enterochromaffin (EC) cells transduce both chemical and mechanical signals and produce 5-hydroxytryptamine to mediate disparate physiological responses. However, the molecular and cellular basis for functional diversity of ECs remains to be adequately defined. Here, we integrated single-cell transcriptomics with spatial image analysis to identify 14 EC clusters that are topographically organized along the gut. Subtypes predicted to be sensitive to the chemical environment and mechanical forces were identified that express distinct transcription factors and hormones. A <i>Piezo2<sup>+</sup></i> population in the distal colon was endowed with a distinctive neuronal signature. Using a combination of genetic, chemogenetic, and pharmacological approaches, we demonstrated <i>Piezo2<sup>+</sup></i> ECs are required for normal colon motility. Our study constructs a molecular map for ECs and offers a framework for deconvoluting EC cells with pleiotropic functions.
Potentially related datasets 4
These accessions were text-mined from the PMC full text. They may be referenced for comparison, cited from other studies, or otherwise mentioned without being primary data for this paper.
| Accession | Source | Title |
|---|---|---|
| GSE92332 | GSE · GEO GEO ↗ | A single-cell survey of the small intestinal epithelium |
| GSE125970 | GSE · GEO GEO ↗ | Single-cell transcriptome analysis reveals differential nutrient absorption functions in human intestine |
| GSE74672 | GSE · GEO GEO ↗ | Single-cell RNA-seq of mouse hypothalamus |
| PRJNA623218 | PRJNA · BioProject | No title in the index |
Funding 3 grants
| Grant | Funder |
|---|---|
| F32 HL143978 | NHLBI NIH HHS (United States) |
| P30 CA023100 | NCI NIH HHS (United States) |
| F32HL143978 | NIH HHS (United States) |