How fish intestinal cells responded to dietary methylmercury exposure? A single-cell transcriptomic analysis

Fish intestine is not only an important digestive and immune organ, but also serves as the first barrier to defend against methylmercury (MeHg) toxicity. Numerous studies have examined the responses of intestine to MeHg, whereas the heterogeneous responses of intestinal cells have not been addressed. In this study, the gilthead seabream were exposed to dietary MeHg, and the gene expression profiles of different intestinal cell populations were examined using scRNA-seq technique. We demonstrated that among the 14 cell types identified, enterocytes, macrophages, T cells and goblet cells were the primary target cell populations exhibiting specific responses to MeHg. Enterocytes appeared to play the most important role in the MeHg transport across the intestinal epithelium as well as intracellular storage. The immune pathways of macrophages and T cells were suppressed by MeHg, which also interfered with the mucus production and secretion in the goblet cells. Furthermore, MeHg not only affected the cell-cell adhesion of the target cells, but also resulted in disorder of lipid metabolism and immune function, thereby leading to increased susceptibility to pathogenic infections. This study provides an important understanding of the specific responses of intestinal cells to MeHg exposure at the cellular level. © 2025 Elsevier Ltd.