For a long period of time, intestinal mesenchymal stromal cells (IMSC) have been considered as a relatively simple and homogeneous group of cells. These cells could effectively regulate intestinal homeostasis and epithelium integrity via producing growth factors and cytokines (Powell et al., 2011). With the help of single-cell transcriptomics studies, it has now been clear that IMSC are quite complex and heterogeneous (Kinchen et al., 2018). However, the detailed cellular and molecular mechanisms that regulate the function of these cells remain poorly understood. Therefore, the ability to perturb and evaluate the in vivo function of IMSC is critical to the understanding of intestinal stem cell niche and the etiology of the inflammatory bowel diseases as well as colitis-associated colorectal cancer.