Extended Data Fig. 1: Tet2^−/− mice display variability in PMP penetrance that correlates with bacteraemia.

a, Penetrance of PMP assessed by splenomegaly, splenic LSK cell expansion and CD11b⁺Gr1⁺ myeloid cell expansion in spleen and peripheral blood. b–e, Correlation between frequency of peripheral-blood CD11b⁺Gr1⁺ myeloid cells (peripheral-blood biomarker) and numbers of CD11b⁺Gr1⁺ myeloid cells in spleen (b) and peripheral blood (c), numbers of LSK cells (d) and splenomegaly (e), in Tet2^+/+ and Tet2^−/− mice. In b–e, dotted vertical lines indicate level of 16% for peripheral-blood CD11b⁺Gr1⁺ myeloid cells (level determined by the distribution in wild-type littermates). The peripheral-blood biomarker (frequency of CD11b⁺Gr1⁺ myeloid cells) was used to categorize Tet2^−/− mice either as symptom free (≤16% CD11b⁺Gr1⁺ myeloid cells) or as mice with PMP (>16% CD11b⁺Gr1⁺ myeloid cells). Spearman correlation test excluding Tet2^+/+ mice. Red lines indicate regression line calculated for Tet2^−/− data points (n = 10 (blue), 23 mice (red). f–i, Symptom-free, Tet2^−/− mice with PMP and littermate controls were used. f, Representative dot blots are shown of LSK cells in the spleen, CD11b⁺Gr1⁺ myeloid cells in the spleen and peripheral blood, and lymphocytes in peripheral blood. Data are representative of five independent experiments with similar results. g, Spleen weight (top; n = 11 (blue), 9 (red, PMP) or 5 mice (red, symptom free)) and numbers of CD11b⁺Gr1⁺ myeloid cells in the spleen (bottom; n = 10 (blue), 12 (red, PMP) or 7 mice (red, symptom free)). h, Numbers per ml of peripheral blood of live CD45⁺ gated white blood cells (WBC) (top left), lymphocytes (top right), CD11b⁺ monocytes (bottom left) and CD11b⁺Gr1⁺ myeloid cells (bottom right) (n = 15 (blue), 15 (red, PMP) or 32 mice (red, symptom free)). i, In vitro HSC self-renewal colony-forming assay of haematopoietic progenitors of the bone marrow (n = 3 mice). Mean ± s.e.m. j, k, Correlation between 16S gene copies in the peripheral blood and spleen weight (n = 16 mice) (j) or numbers of CD11b⁺ monocytes (k top left), percentage of lymphocytes (k top right), numbers of lymphocytes (k bottom left), and numbers of leukocytes (WBC) (k bottom right) in the peripheral blood (n = 40 mice). Pearson correlation test. l, Bacterial colonies from Fig. 1e, f identified by 16S sequencing; blue rectangles indicate presence of bacteria. In g, h, boxes represent median values and interquartile ranges; whiskers represent minimum and maximum values. One-way ANOVA, Sidak’s post hoc test. Data are representative of at least three independent experiments. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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