Notch signalling regulates asymmetric division and inter-conversion between lgr5 and bmi1 expressing intestinal stem cells

Rapidly cycling LGR5+ intestinal stem cells (ISCs) located at the base of crypts are the primary driver of regeneration. Additionally, BMI1 expression is correlated with a slow cycling pool of ISCs located at +4 position. While previous reports have shown interconversion between these two populations following tissue injury, we provide evidence that NOTCH signaling regulates the balance between these two populations and promotes asymmetric division as a mechanism for interconversion in the mouse intestine. In both in vitro and in vivo models, NOTCH suppression reduces the ratio of BMI1+/LGR5+ ISCs while NOTCH stimulation increases this ratio. Furthermore, NOTCH signaling can activate asymmetric division after intestinal inflammation. Overall, these data provide insights into ISC plasticity, demonstrating a direct interconversion mechanism between slow- and fast-cycling ISCs.