Telocytes: Active Players in the Rainbow Trout (Oncorhynchus mykiss) Intestinal Stem-Cell Niche

SIMPLE SUMMARY: Aquaculture is expanding due to the high demand of fish for human consumption. However, since carnivorous fish are fed using fish-derived proteins and lipids, the sustainability of this food-producing sector is debated. Therefore, feed industries and academia are dedicating their efforts to the search for suitable raw materials and more sustainable alternative feeds that are able to ensure the health of the fish. To properly evaluate the effect of these feed formulations, extensive knowledge of the intestinal morphology and physiology is required. Moreover, the intestine is a dynamic environment in which homeostasis is controlled by highly specialized intestinal stem-cell niches. These defined functional units consist of epithelial stem cells, the supportive mesenchymal cell population, and acellular components. While they have been widely studied in the mouse intestine, this understanding is almost absent in fish species. We have previously characterized the organization of the stem-cell niche in the rainbow trout intestine; here, we expand that knowledge by examining telocytes as active stromal components of the niche. Our results indicate that this cell type is also present in rainbow trout and that it represents a key mediator of intestinal homeostasis by virtue of its active interaction with the stem cells. ABSTRACT: In order to improve the sustainability of trout farming, it is essential to develop alternatives to fish-based meals that prevent intestinal disorders and support growth performances. Therefore, an accurate knowledge of intestinal morphology and physiology is desirable. We previously described the epithelial component of the intestinal stem-cell (ISC) niche in rainbow trout (Oncorhynchus mykiss), which is one of the most successfully farmed species and a representative model of the salmonids family. This work aims to expand that knowledge by investigating the niche stromal components that contribute to intestinal homeostasis. We analyzed samples belonging to five individuals collected from a local commercial farm. Histological and ultrastructural studies revealed peculiar mesenchymal cells adjacent to the epithelium that generated an intricate mesh spanning from the folds’ base to their apex. Their voluminous nuclei, limited cytoplasm and long cytoplasmic projections characterized them as telocytes (TCs). TEM analysis showed the secretion of extracellular vesicles, suggesting their functional implication in cell-to-cell communication. Furthermore, we evaluated the localization of well-defined mouse TC markers (pdgfrα and foxl1) and their relationship with the epithelial component of the niche. TCs establish a direct connection with ISCs and provide short-range signaling, which also indicates their key role as the mesenchymal component of the stem-cell niche in this species. Interestingly, the TC distribution and gene-expression pattern in rainbow trout closely overlapped with those observed in mice, indicating that they have the same functions in both species. These results substantially improve our understanding of the mechanisms regulating intestinal homeostasis and will enable a more detailed evaluation of innovative feed effects.