Gene expression profile of mouse intestinal epithelial cells during homeostasis and villus atrophy at single-cell resolution

The epithelium that lines small intestinal villi is critically important for nutrient absorption, defense against pathogens, and mucosal homeostasis. Atrophy or blunting of the villi as a result of epithelial damage is commonly observed in celiac disease, viral gastroenteritis, and various other pathologies. Whereas adaptive responses during epithelial stem cell injury are increasingly well understood, how epithelial tissues, and particularly the intestine, cope with drastic loss of differentiated cells remains unclear. Using an acute model of viral gastroenteritis induced by poly(I:C), we aimed to dissect the cellular adaptations that follow severe intestinal villus injury. Single-cell transcriptional profiling of intestinal epithelial cells was performed using the 10x Genomics platform on two separate sets of samples: (1) wild-type mice during homeostasis and villus atrophy, two replicates each; (2) Yap WT and Yap KO mice during villus atrophy, two replicates each. The villus atrophy samples from the first set were taken just from the damaged region of the gut, whereas the villus atrophy samples from the second set were taken from both the damaged and distal non-damaged region of the gut.