Shifting paradigms in tissue stem cell biology: Insights from the intestine

The small intestinal epithelium represents the most rapidly self-renewing adult mammalian tissue, with a turnover time of 1–2 weeks. It contains ∼12 easily recognizable cell types with a wide diversity of functions, including nutrient absorption, mucus production, antimicrobial defense, and the regulation of metabolism by incretins like Glp1. The simple and repetitive crypt-villus architecture allows for easily interpretable experimentation in transgenic mice in vivo , while the human stem cell hierarchy is experimentally accessible in epithelial organoids in vitro . This review aims to comprehensively describe the design, the cellular constituents, and the molecular regulation of crypt-villus epithelial self-renewal. More generally, it highlights deviations from commonly held views on tissue stem cell biology: gut stem cells divide continually and symmetrically. They can be expanded indefinitely in vitro , while the plasticity of daughter cells can recreate stem cells during regeneration.