Fig. 2: Deletion of Tsc1 in Lgr5⁺ ISCs leads to villus premature aging.

a A schematic for conditional ablation of Tsc1 and RAP treatment in Lgr5-CreERT;Tsc1^f/f mice (b–e). b H/E and Ki67 staining showed that ablation of Tsc1 in Lgr5⁺ ISCs led to crypt overgrowth at 2 months of age and deterioration of villus structure (the midline section of the proximal jejunum) at 8 months of age, which were partially rescued by RAP. Right panels: quantification data (mean ± SEM). N = 8 mice per group. **P < 0.01 (determined using Student’s t test). c Eight-month-old Lgr5-CreERT;Tsc1^f/f mice showed decreased nutrient absorption activities for L-glucose (mmol/l), amino acids (ng/ml), and fatty acids, which were partially rescued by RAP treatment. Data are expressed as mean ± SEM. N = 5 mice per group. *P < 0.05, **P < 0.01 (determined using Student’s t test). d, e Eight-month-old Lgr5-CreERT;Tsc1^f/f mice showed increased sensitivity to IR-induced decreases in the numbers of crypts and proliferating cells at day 2 post IR (d), and compromised regeneration (decreases in the height and number of villi and crypts) at day 6 post IR (e), which were partially rescued by RAP treatment. Data are expressed as mean ± SEM. N = 5 mice per group. *P < 0.05, **P < 0.01 (determined using Student’s t test).