Control of Paneth cell function by HuR regulates gut mucosal growth by altering stem cell activity

HuR stimulates the activity of intestinal stem cells by enhancing Paneth cell function via activation of mitochondrial metabolism, thus promoting renewal of the intestinal mucosa To obtain cell type-specific transcriptional regulation profiles in the intestinal epithelium after HuR deletion, we performed single-cell RNA-sequencing (scRNA-seq) analysis on the small intestinal mucosa harvested from IE-HuR−/− and control littermate mice. In total, 60,000 high-quality cells were grouped into 18 clusters, which expressed classic cell type markers from the absorptive or secretory lineages, and markers distinctive of ISCs and daughter transient-amplifying cells), following published single-cell transcriptomic signatures in the intestinal epithelium. Secretory cells in the epithelial compartment of the small intestine consisted of PCs, goblet cells, tuft cells, and enteroendocrine cells in both IE-HuR−/− and littermate mice, whereas absorptive cells were marked by various enterocytes. Cell cluster analysis revealed that the numbers of PCs and ISCs decreased in IE-HuR−/− mice compared with control littermate mice, which were consistent with the findings obtained from studies using immunostaining assays.