The primary cilia of the gastrointestinal tract in homeostasis and disease at the single-cell level

Abstract

The gastrointestinal tract is regularly renewed by stem cells which divide and differentiate into functionally and morphologically distinct cell types. Several key pathways, such as Wnt, Hedgehog and Bmp, regulate the cell fate. However, it remains a mystery how the associated signaling molecules are relayed between cells to coordinate stemness and differentiation cues. Primary cilia are small antenna-like organelles that harbors many receptors for these pathways. Here public single-cell RNA sequencing data is re-analyzed to show that primary cilia expression is heterogeneous in the intestinal mesenchyme and liver. Presence of primary cilia is also validated using immunofluorescence in the stroma and muscle cells of the mouse colon, using known markers of the primary cilia. Acot7 is identified as a primary cilium associated marker and found to be expressed in myenteric ganglia. In mice challenged with DSS to model ulcerative colitis, primary cilia are observed more abundant as the area covered by crypt structures become reduced due to the loss of epithelium. Acot7 expressing ganglial cells were observed more frequently and displayed morphological differences. Additionally, mice fed a high-fat diet over 16 weeks had shortening of the colon crypts and an increase in the primary cilia. This work suggests that primary cilia exist in the gastrointestinal tract during homeostasis and participate in inflammation and diet-based adaptations.