Extended Data Fig. 1: Loss of intestinal epithelial integrity contributes to pre-leukaemic HSC expansion.

a,b, The gut microbiota of high-dose (8 Gy) (a) and low-dose (2.5 Gy) (b) irradiated mice were analysed for alpha-diversity, including observed operational taxonomic units (OTUs) and Shannon indices. c, Colon length in low-dose irradiated mice (n = 6 mice per time point). d, Intestinal permeability of low-dose irradiated mice measured by FITC-dextran translocation to the plasma following oral gavage (n = 6 mice per time point). e, Bacterial 16S gene copies measured in PB of low-dose irradiated mice (n = 4 mice per time point). f, Histological staining of distal colons (upper panel) and BM (lower panel) at the indicated weeks post-irradiation. Scale bars: 100 μm. Data are representative of 4 independent experiments. g, Experimental design to examine the effect of irradiation. Chimeric mice were generated by irradiating the recipient mice at either high-dose (8 Gy) or low-dose (2.5 Gy), and flow cytometry was performed on BM. Secondary transplants were performed with purified donor HSCs (CD45.2+). h, Number of donor HSCs (Lin-cKit+Sca1 + CD150 + CD48-) in the BM. Error bars represent the SEM. (n = 7 low-dose irradiated mice per group; n = 6 high-dose irradiated mice per group). i,j, Donor-derived proportions in the PB of recipient mice transplanted with low-dose irradiated (i), and high-dose irradiated mice (j) (n = 11 mice per group). Error bars represent the SEM. P values were calculated for the indicated comparisons using a two-tailed unpaired Student’s t-test (a and h) and a two-way ANOVA (b, c, d, e, i, and j).

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