Lgr5+ intestinal stem cells (ISCs) drive the fast renewal of intestinal epithelium. Several signaling pathways have been shown to regulate ISC fates. However, it is unclear what are the essential signals to sustain the ISC self-renewal. Using genetic and single-cell RNA-sequencing approaches, we observed the critical roles of BMP and stromal cells in maintaining ISC self-renewal and epithelial homeostasis. We have also constructed a spatiotemporal transcriptomic landscape of the mouse stomach and intestine during embryonic day E9.5-E15.5. The regionalization and heterogeneity of both the epithelium and mesenchyme could be traced back to E9.5. The spatiotemporal distributions of cell clusters and the mesenchymal-epithelial interaction analysis indicate that a coordinated development of the epithelium and mesenchyme contribute to the stomach regionalization, intestine segmentation and villus formation.