Fig. 5: Metabolic interventions to treat ulcerative colitis.
From: Metabolic adaptations direct cell fate during tissue regeneration
a, ABP staining and immunofluorescence for OGDH, Ki67 and 5hmC in colon samples from mice with or without colitis induced by DSS. Dashed lines outline colonic crypts. b, ABP levels and OGDH expression over time in mice treated with DSS (n ≥ 5). The box represents the IQR and the central line represents the median. Whiskers extend to 1.5 × IQR beyond Q1 and Q3. R, recovery (15 days). c, Relationship between αKG levels (measured by LC–MS from colonic samples) and secretory cell abundance (measured as number pixels of ABP staining) in DSS-treated mice over time (n ≥ 4 per time point and condition). d, ELISA from whole-colon lysates to measure 5hmC abundance in DSS-treated mice. Each dot represents one mouse (n ≥ 4). e, Body weight (relative to initial body weight) in the indicated conditions (vehicle n = 4, shOgdh n = 5, DSS n = 7, DSS + shOgdh n = 11). f, Haematoxylin and eosin (H&E) and ABP staining of colonic samples isolated from DSS-treated mice or DSS-treated mice with pulsatile OGDH inhibition at day 9. g, Body weight under the specified conditions, relative to body weight at baseline (vehicle n = 30, αKG n = 15, DSS n = 35, DSS + αKG n = 15). h, H&E and ABP staining of colonic sections from DSS-treated or DSS-and-αKG-treated mice at day 9. i, Multiplex immunofluorescence under the specified conditions, revealing the architecture and cell composition of the tissue microenvironment, epithelial compartment and epigenetic landscape in DSS-and-αKG-treated-treated mice. CK, pan-cytokeratin; Vim, vimentin; αSMA, α-smooth muscle actin. Scale bar, 50 μm. j, Experimental design to trace secretory progenitors (ATOH1+ cells) using an Atoh1-CreERT2 line crossed with an LSL Kate reporter mouse. i.p., intraperitoneal; Tam, tamoxifen. k, Immunofluorescence for Kate (progeny of ATOH1+ cells) and EphB2 (colonic stem cells) under the specified conditions. The dashed lines indicate the boundary between DSS and DSS + αKG intestines within the same slide. Scale bar, 400 μm. This figure is adapted from our published patent (WO2024229094A1)50. Data are mean ± s.e.m. Statistical significance was determined by one-way ANOVA followed by Tukey’s HSD test in b,d and two-way ANOVA followed by Tukey’s HSD test in e,g.
