Extended Data Fig. 8: The crypts with high DNAm drift have altered iron homeostasis and the TET enzymatic activity.

a, hMeDIP analysis of the Dkk2 gene promoter in the intestinal crypts isolated from young and old mice. n = 3 mice per group were analyzed. p-value was calculated by Welch’s t-test, 2-tails. b, hMeDIP analysis of the Sfrp1 gene promoter in the intestinal crypts isolated from young and old mice. n = 3 mice per group were analyzed. p-value was calculated by Welch’s t-test 2-tails. c, Schematic representation of functional experiments using organoid culture. d, hMeDIP analysis of the Dkk2 and the Sfrp1 gene promoters in the organoids treated with the C35 TET inhibitor for 1 week. n = 3 mice per group were analyzed. p-value was calculated by Welch’s t-test, 2-tails. e, Bar chart showing the DNAm level of the Sfrp1 gene promoter analyzed by BS pyrosequencing at the indicated time points upon the C35 TET inhibitor treatment of organoids derived from young intestinal crypts. n = 3 mice per group were analyzed. p-value was calculated by Welch’s t-test, 2-tails. f, Bar charts showing the DNAm level of the Sfrp1 and Sfrp2 gene promoters in intestinal crypts isolated from WT and Tet2/3-dKO mice. n = 3 mice per group were analyzed. p-value was calculated by Welch’s t-test, 2-tails. g, Bar chart showing the DNAm level of the Sfrp1 gene promoter analyzed by BS pyrosequencing in organoids treated with the iron chelator desferoxamine (DFO) for 1 and 2 months. n = 3 mice per group were analyzed. p-value was calculated by paired t-test, 2-tails. h, Bar chart showing the DNAm level of the Sfrp1 gene promoter analyzed by BS pyrosequencing in the intestinal organoids as in Fig. 6a. Parental organoids = untransduced organoids at day 0. n = 3 mice per group were analyzed. p-value was calculated by Welch’s t-test, 2-tails. Error bars in the figure bar charts represent the SD.