Figure 2.

Kras G12D mutation in HSC causes expansion of multipotent and lymphoid-primed progenitors. Pdzk1ip1-CreER R26Tom/Tom reporter mice with WT or conditional mutant (KrasG12D) Kras alleles were administered tamoxifen to induce simultaneous Tom expression and Kras mutation in HSC. Stem/progenitor populations in the BM were analyzed at the indicated time points after tamoxifen treatment. (A) Fractions of Tom+ stem/progenitor cell populations. Symbols represent individual mice; bars represent the mean ± SD of data from a single experiment (2 and 5 wk) or from two experiments (3 wk). (B) Absolute numbers of Tom+ stem/progenitor cell populations. Symbols represent individual mice; bars represent the mean ± SD of data from a single experiment (2 and 3 wk) or from two experiments (5 wk). The data correspond to (2 wk) or partially overlap (3 and 5 wk) those in panel A. (C–F) Expression of IL-7R on Flt3+ progenitors in WT or KrasG12D reporter mice at 3 wk after tamoxifen administration. (C) Representative staining of the Lin population from a KrasG12D reporter mouse, highlighting Flt3+ MPP4 within the gated LSK cells, and Flt3+ cells with negative (neg), intermediate (int), or high (hi) levels of c-Kit within the gated Sca-1 cells. (D) Representative histograms of IL-7R expression on total Flt3+ progenitors defined in panel C from WT (gray, top row) or KrasG12D (red, bottom row) reporter mice. (E) Fraction of IL-7R+ cells among the total gated Flt3+ progenitors in WT or KrasG12D reporter mice. (F) Fraction of Tom+ cells among the gated Flt3+ IL-7R+ progenitors in WT or KrasG12D reporter mice. In panels E and F, symbols represent individual mice; bars represent the mean ± SD of data from two experiments. Statistical significance was estimated by the Mann–Whitney test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.

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