Transcriptome profiles of telocytes along the intestinal crypt-villus axis

Background & aimsIntestinal epithelial cells rely on a complex array of signals from the stromal microenvironment to determine their fate and function along the crypt-villus axis, but the precise cellular sources and combinations of signals regulating each position remain poorly defined. MethodsHere, we present a high-resolution atlas of a unique mesenchymal cell type previously identified as telocytes, mapped along the crypt-villus axis using single-cell RNA sequencing integrated with in-situ approaches and reporter mouse models. ResultsWe identify four spatially distinct telocyte subtypes: crypt, villus base, villus mid and villus tip, each with a unique gene expression profile. Crypt telocytes are enriched for canonical Wnt signaling components that support stem and progenitor cell maintenance, while villus base telocytes are a source of Bmps (bone morphogenic proteins) and express contractility-associated genes, suggesting a role in tissue architecture. Villus mid telocytes display signatures of immune regulation and inflammation, while villus tip telocytes are specialized for the regulation of ribonucleoprotein complexes and nutrient sensing. ConclusionsThis atlas provides a foundational resource for understanding how diverse telocyte populations coordinate signaling environments and shape intestinal homeostasis through both epithelial interactions and extensive crosstalk among themselves.