Extended Data Fig. 1. NPM1 deficiency increases susceptibility to enteritis and colonic adenocarcinoma.
(a) UMAP analysis of GSE182270 shows different clusters of cells in human colonic biopsies. (b) Expression of NPM1 in different clusters (y axis). Dot size represents the fraction of cells within the cluster that express each NPM1. Colors indicate the z-scaled expression of genes in cells within each cluster. (c) Expression of NPM1 in different stages of 425 COAD patients in TCGA. (Stages I and II: n = 238 individual patients; stages III and IV: n = 187 individual patients). (d) Survival analysis of NPM1 in 270 COAD patients in TCGA, cutoff by the median expression of NPM1 in groups. (e) Survival analysis of NPM1 in 92 READ patients in TCGA, cutoff by the median expression of NPM1 in groups. (f,g) Protein expression analysis of NPM1 in the colon of Npm1+/+ and Npm1+/− mice. Quantitative analysis of protein levels of NPM1, relative to tubulin (e) (n = 3 individual mice). (h) RT-PCR analysis of mRNA expression of Npm1 in whole colon of Npm1+/+ and Npm1+/− mice (n = 7 individual mice). (i) Representative images of colons from Npm1+/+ and Npm1+/− mice in steady state. (j) H&E staining of colon from Npm1+/+ and Npm1+/− mice in steady state. Scale bars: 100 μm. (k) Comparison of mesenteric lymph nodes from Npm1+/+ and Npm1+/− mice in steady state (n = 4). (l,m) Representative images of Peyer’s patches from Npm1+/+ and Npm1+/− mice in steady state (l). Analysis of the number of Peyer’s patches (m) was performed (n = 5 individual mice). (n) H&E staining of solitary intestinal lymphoid tissue from Npm1+/+ and Npm1+/− mice in steady state. Scale bars: 100 μm. (o) Ratio of LK, LSK, Lin−Sca1low CD117low cells (Npm1+/+: n = 7 individual mice; Npm1+/−: n = 6 individual mice), CMP, GMP and MEP (Npm1+/+: n = 5 individual mice; Npm1+/−: n = 6 individual mice) in bone marrow from Npm1+/+ and Npm1+/− mice under steady-state. (p) Ratio of LK, LSK, Lin−Sca1low CD117low cells, CMP, GMP and MEP in bone marrow from Npm1+/+ and Npm1+/− mice under steady-state (n = 6 individual mice). (q–u) Npm1+/− and control Npm1+/+ mice were administered trinitrobenzene sulfonic acid (TNBS). Colon length (q,r), colon histopathology on day 7 (s), body weight (t) and DAI (u) were analyzed (n = 5 individual mice). Scale bars: 500 μm (up), 100 μm (down). (v,w) Npm1+/− and control Npm1+/+ mice were treated with AOM-DSS for 65 days, and body weight (v) and DAI (w) were analyzed (n = 5 individual mice). (x) Representative images of colons from CRC mouse model. Data in c, g, h, m, o, p and r are representative of two independent experiments, shown as the means ± s.e.m., and statistical significance was determined two-tailed unpaired Student’s t-test (*p < 0.05, **p < 0.01 and ***p < 0.001).