Roles of intestinal stem cells in inflammatory bowel disease pathogenesis

Figure 2 Key signaling pathways orchestrate stem cell fate regulation. At the crypt base, mesenchymal cells and Paneth cells secrete Wnt ligands and R-spondins to sustain the stemness and proliferation of intestinal stem cells (ISCs). Mesenchymal cells also produce bone morphogenetic protein inhibitors, promoting the self-renewal of ISCs. Epidermal growth factor, derived from Paneth cells, promotes ISC proliferation, survival, and long-term organoid growth. In addition to Wnt and epidermal growth factor, Paneth cells provide critical Notch signals to ISCs, with Notch signaling orchestrating the balance between absorptive and secretory lineage commitment. Images created with BioRender.com (Supplementary material). BMP: Bone morphogenetic protein; EGF: Epidermal growth factor; RSPOs: R-spondins.