Extended Data Fig. 1: Characterization of OGDH expression in the gut.

a, UMAP derived from publicly available scRNA-seq data demonstrating distinct transcriptional signatures in various subpopulations of human intestinal and colonic cells. b, AddModule Score showing average expression of the TCA-cycle signature across the indicated intestinal lineages human small intestine. Each dot represents a cell. c, Dot plot showing TCA-cycle enzyme gene expression across intestinal cell types from publicly available scRNA-seq data. Colour intensity indicates expression levels and dot size indicates the percentage of positive cells in each lineage. Paneth cells were sorted as GFP-, FSC-A-high and ISCs were sorted as GFP-high from Lgr5-EGFP reporter mice. d, Single-molecule in situ fluorescence (smFISH) visualizing RNAs of the indicated TCA-cycle enzymes in intestinal tissue samples from C57Bl/6 mice. Dashed lines outline crypt structure and specific lineages within the crypt. e, Representative immunofluorescence results from intestinal tissues from Lgr5-EGFP mice showing GFP (LGR5; marking ISCs), OGDH, Lyz (Paneth cells) and ACE2 (enterocytes). f, Quantification of the percentage of OGDH-expressing cells in the indicated intestinal lineages. Each dot represents a mouse (enterocytes n = 17; ISCs n = 9; Paneth cells n = 9). g–i, Receiver operating characteristic (ROC) curve analysis assessing the sensitivity and specificity of OGDH as a marker of enterocytes (g), ISCs (h) and Paneth cells (i). Statistical analysis: data are presented as mean ± s.e.m. The box represents the interquartile range (IQR) with the median as a central line. Whiskers extend to 1.5×IQR beyond Q1 and Q3. This figure is adapted from our published patent (WO2024229094A1)⁵⁰. Significance was determined by Wilcoxon test in b (see Supplementary Table 1), one-way ANOVA followed by Tukey’s HSD test in f and Wilson/Brown test in g–i. Asterisks indicate statistical significance (*P < 0.05, **P < 0.01, ***P < 0.001).

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