Fig. 4: Effects of (pre-)leukemic mutations on cellular differentiation.

See also Supplementary Fig. 8. a Clonal identity of the cells from P1 highlighted on the uMAP (Figs. 2b, e, 3a). Gray dots correspond to cells from other patients. The dotted ellipse serves as a guide to identify the location of the HSC/MPP population. b Clonal identity of the cells from P2 highlighted on the uMAP (Figs. 2c, f, 3a). c Observed variant allele frequencies for the IDH2 R88Q mutation from P3 highlighted on the uMAP. Small black dots correspond to cells with no coverage of the mutation (see Supplementary Fig. 8a for an estimate of target capture rates). d Observed variant allele frequencies for the synonymous NUP188 mutation from P4 highlighted on the uMAP. This mutation was observed at an allele frequency of 50% in exome data of total bone marrow. Note that CD34+ cells were enriched more than 100-fold during sorting for single-cell RNA-seq (Supplementary Fig. 2 and see Supplementary Fig. 8a for an estimate of target capture rates). e Estimate of the contribution of different clones to the cell types. For P1 and P2, clonal identities from Fig. 2 were used. For P3, cell were classified as leukemic if the IDH2 mutation was observed, as pre-leukemic if the SRSF2 mutation was observed, or as non-leukemic if the reference allele was observed for both mutations. Cells without coverage were excluded from the analysis. For P4, cells were classified as leukemic if the NUP188 mutation was observed, or as non-leukemic if the reference allele was observed. Bars are only shown for populations covered with at least 10 cells (see Supplementary Fig. 8b for absolute numbers and Supplementary Fig. 8c, d for a quantitative analysis).