Figure 5.
Model for ISC self-renewal and differentiation. (a) Under physiological conditions, the self-renewal and differentiation of ISCs is controlled by the cooperation of Wnt and Notch pathways. (b) When Lgr5+ stem cells are cultured in vitro, CHIR activates the Wnt pathway and inhibits enterocyte differentiation, whereas VPA alone or together with CHIR suppresses secretory cell specification. The combination of CHIR and VPA maintains ISCs in an undifferentiated, self-renewing state. Additional combinations of inhibitors promote various intestinal cell fates as shown.