Fig. 4. Adaptation of surface protein expression in healthy aging and cancer.
a, Correlation of surface marker expression between matched cell types from aged and young BM donors. For each cell type, mean surface marker expression across all cells was computed, separately for all ‘young’ and ‘aged’ samples. Left panel: histogram of Pearson correlation coefficients. Right panel: sample scatter plots depicting the mean surface expression of all measured markers in indicated cell types. b, Volcano plot depicting log2 fold change and false discovery rate (FDR) for a test for differential surface marker expression between cells from young and aged individuals, while accounting for cell types as covariates. See Methods for details. c, Boxplots depicting CD27 surface expression in naïve T cell populations from young and aged individuals. Sample size is provided as Figure Source Data. See Methods, section Data visualization for a definition of boxplot elements. d, Projection of AML samples onto healthy reference. See Supplementary Note 7 for details. e, Clustering of leukemia samples by their projected cell type composition. Lymphoid cells are excluded from the clustering. f, Density plots of monocyte pseudotime, resulting from projection on the healthy reference. See Methods for details. g, Heatmap depicting surface markers with differential expression between the phenotypic classes defined in e. The eight markers with the most significant P values from DESeq2 were selected for each comparison between classes. Average expression across all nonlymphoid cells is shown. ITD, internal tandem duplication; mut, mutation; wt, wild type. h, Surface expression of immunotherapy targets CTLA4 (CD152) and PD-L1 (CD274) in different myeloid compartments of healthy donors and AMLs. Sample size is provided as Figure Source Data. i, Scatter plot depicting the average expression of all surface markers in healthy HSCs and MPPs (x axis) and leukemic stem cells (LSC) projecting to the HSC and MPP cell state (y axis). Cells from four patients where the HSC/MPP class was covered with more than 20 cells are included (AML1, AML2, AML3 and AML Q6). P values for differential expression were computed using DESeq2 and are encoded in the symbol size, and previously described LSC markers are depicted as a triangle. Interpatient variability is color-coded, see Methods, for details. See also Supplementary Data 2.