Lgr5+ telocytes are a signaling source at the intestinal villus tip

Abstract

The intestinal epithelium is a structured organ composed of crypts harboring Lgr5+ stem cells, and villi harboring differentiated cells. Spatial transcriptomics have demonstrated profound zonation of epithelial gene expression along the villus axis, but the mechanisms shaping this spatial variability are unknown. Here, we combine laser capture micro-dissection and single cell RNA sequencing to uncover spatially zonated populations of mesenchymal cells along the crypt-villus axis. These include villus tip telocytes (VTTs) that express Lgr5, a gene previously considered a specific crypt epithelial stem cell marker. VTTs are elongated cells that line the villus tip epithelium and signal through Bmp morphogens and the non-canonical Wnt5a ligand. Their ablation is associated with perturbed zonation of enterocyte genes induced at the villus tip. Our study provides a spatially-resolved cell atlas of the small intestinal stroma and exposes Lgr5+ villus tip telocytes as regulators of the epithelial spatial expression programs along the villus axis.

Defining human mesenchymal and epithelial heterogeneity in response to oral inflammatory disease

“…In the mesenchymal lineage, we identified populations of established cells, such as myofibroblasts and pericytes, and five additional distinct populations of fibroblast-like cells. Recent studies have started to elucidate the role of stromal cell populations in tissue homeostasis (Shoshkes-Carmel et al, 2018, Bahar Halpern et al, 2020, Greicius et al, 2018), and consistent with previous studies we identified two populations expressing Wnts and Wnt inhibitors suggesting the presence of mesenchymal niche regulating populations (Kinchen et al, 2018, Kim et al, 2020) that may be required for oral mucosa maintenance. In periodontitis, we observed that these populations were preserved in the mild stage, whereas the myofibroblast and pericyte populations were strikingly reduced.…”

Morphological and immunohistochemical phenotype of TCs in the intestinal bulb of Grass carp and their potential role in intestinal immunity

“…TCs are identified in a wide variety of organs from diverse species including mammals 8 – 11 , avian 12 , 13 , reptiles 14 , Amphibians 15 and aquatic species 16 , 17 and parasitic worm 18 . They are located in the trachea and lungs 19 , heart 20 and the blood vessels 21 , kidney, ureter, urinary bladder 22 , tongue 23 , oesophagus, stomach and small and large intestines 24 , liver , pancreas 14 , testis 25 , prostate 26 , efferent ductules 27 ovaries, oviducts, uterus, vagina, mammary glands and placenta 26 , spleen 8 , 28 .…”

Distinct populations of crypt-associated fibroblasts act as signaling hubs to control colon homeostasis

“…CTFs show an enrichment for the regulon activities of Lef1, Runx1, https://doi.org/10.1371/journal.pbio.3001032.g002 The transcription factor Nkx2-3 had previously been found to control Bmp2/4 expression in the small intestine [21]. Lef1 regulon activity in CTFs may hint at a possible explanation for the presence of the recently discovered small intestinal Lgr5 + villus tip telocytes [22], given that Lgr5 is canonical Wnt targe gene [23], and Lef1 is both a canonical Wnt target gene and a Wnt/b-catenin transcription factor [24]. Intriguingly, this would also point to a difference in transcriptional regulation of Lgr5 + mesenchymal cells compared to Lgr5 + intestinal stem cells, which have been shown to mainly depend on TCF family member Tcf4 [25].…”