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. 2021 Mar 10;12:638725. doi: 10.3389/fimmu.2021.638725

Figure 1.

Figure 1

Overview of the intestinal stem cell compartment and molecular cascades related to AhR signaling. (A) Active and quiescent stem cells reside at the crypt base in both the small and large intestine. Local morphogenetic factors produced from small intestinal Paneth and subepithelial mesenchymal cells regulate ISC activity. As stimulated ISCs migrate upward into the transit amplifying compartment, they then become committed differentiated cells. A brush border resides at the apical surface of epithelial cells in the small intestine which maximizes the absorptive surface area. In contrast, both Paneth cells and a brush border are absent in the colon. While the absence of Paneth cells in the colon results in decreased antimicrobial proteins, the colon employs other mechanisms to maintain intestinal homeostasis. LGR5 leucine-rich-repeat containing G-protein coupled receptor 5, CBC crypt base columnar. (B) Numerous molecular pathways orchestrate epithelial cell fate in concordance with local morphogenetic factors within the ISC. Key proteins in each signaling pathway (blue) interact with transcription factors (brown) to regulate gene transcription. Upstream of this, additional kinases (orange) modulate these pathways. Both Wnt/β-catenin and Notch signaling play a pivotal role in regulating the differentiation of either secretory or absorptive epithelial cell types. Together with EGF/MAPK and JAK/STAT signaling as well as others, these pathways work in tandem to regulate ISC stemness. Akt protein kinase B, APC adenomatous polyposis coli, Bcat beta catenin, CK casein kinase, CSL CBF1/SU/LAG1, Cyto cytokine, DKK Dickkopf, DSL Delta/Serrate/LAG2 transmembrane ligands, DVL Disheveled, EGF epidermal growth factor, EGFR epidermal growth factor receptor, γ gamma secretase, GAP GTPase-activated protein, GRB2 growth factor receptor-bound protein 2, GSK glycogen synthase kinase, HES1 hairy and enhancer of split 1, JAK/STAT janus kinase/signal transducer and activator of transcription, MAML Mastermind-like, MATH1 Protein atonal homolog 1, mTOR mammalian target of rapamycin, NICD Notch intracellular domain, PI3k phosphoinositide 3-kinase, PKCalpha protein kinase c alpha, RNF43 ring finger 43, Rspo respondins, RTK receptor tyrosine kinase, SHP2 Src homology 2 phosphatase 2, SOCS suppressors of cytokine signaling, SOS son of sevenless, TCF/LEF T-cell factor/lymphoid enhancer-binding factor, Ub ubiquination, ZNRF3 zinc and ring finger 3.