Extended Data Figure 8. TET1 hypomorphic mice present a significantly impaired ductal regeneration upon damage.

a, Graph represents mean ±SD of mouse weight of WT (n=21 mice), Tet1^hypo/+ (n=13 mice) and Tet1^hypo/hypo (n=27 mice) littermates. Student's two tailed t-test statistical analyses were performed. b, Relative mouse weight of WT (n=5), Tet1^hypo/+ (n=1) and Tet1^hypo/hypo (n=5) mice. c, Representative H&E stainings (n=3 experiments) of intestines from 50 week old WT and Tet1^hypo/hypo mice. Scale bar, 100μm. . d, Representative H&E stainings (n=3 experiments) of small intestine from 10 week old WT and Tet1^hypo/hypo mice treated with DDC for 5 days. Scale bar, 100μm. e-f, Box-and-whisker plots showing median and IQR of proliferating ductal cells (OPN⁺/Ki67⁺) (e) or total ductal cells (OPN⁺) (f). Undamaged, n=3 WT and n=3 Tet1^hypo/hypo ; DDC, n=7 WT and n=6 Tet1^hypo/hypo ; Recovery, n=3 WT and n=4 Tet1^hypo/hypo). Dots, outliers. Squares, median level corresponding to each independent mice. p-values obtained by two-sided Kolmogorov-Smirnov test. g, Population distribution of the total number of ductal cells (OPN⁺) Dashed lines show median values obtained from 55 FOV (n=3) for WT and 56 FOV for Tet1^hypo/hypo (n=3) mice at day 0 (undamaged) and 110 FOV for WT (n=3) and 153 FOV for Tet1^hypo/hypo (n=4) mice at day 12 (recovery). h, PCK immunohistochemistry (n=3 experiments) from WT (left) and Tet1^hypo/hypo (right) undamaged or in recovery after DDC (day 12) livers. Nucleus, Haematoxylin. Scale bar, 100μm. i, Lgr5 and Tet1 mRNA levels, TET1 ChIP and hMedIP on Lgr5 TSS were analysed in undamaged and DDC treated livers. Graphs represent mean±SD of values obtained from n=3 independent biological replicates (dot). p-value was calculated using Student's two-tailed t-test.