Figure 4.
Stability of granulopoiesis over time. (A) Heat map showing the natural log fractional abundances of the highest contributing granulocyte (Gr) barcodes (clones) in ZH33 and ZG66 over time, defined as the set of all barcodes present as a top 100 highest contributing barcode in ≥1 of the samples shown. Each row corresponds to 1 barcode. The barcodes are organized by unsupervised hierarchical clustering using the Euclidean distance between barcodes’ log fractional abundances, with relative contribution shown as a red-to-blue gradient, representing high contribution to no contribution, respectively. Clones are clustered along the y-axis to place similar clones next to each other. *Indicates the top 100 clones in a given sample; thus, there are 100 in each column and ≥1 in each row. (B) The Pearson correlations between Gr clonalities at a certain time point post-transplantation and all subsequent Gr clonalities are plotted as individual lines for ZH33 and ZG66. Each time point is shown as a different color line, so, for example, the correlation of the 1-month sample with the 2-month sample is shown by the position of the red line at the 2-month time point on the y-axis. (C) The total clonal repertoires of barcoded granulopoiesis are displayed for ZH33 and ZG66 as cumulative distribution curves (supplemental Data provide more information on the analytic methodology used). Each position on the x-axis is an individual clone, and each line is the cumulative distribution of clonal contributions at the specified time point. Note that although these clones appear as lines, they are actually discrete sets of points (clones). The height of the line at an index on the x-axis is the sum of the clonal contributions of the clones with an index less than or equal to the index in question. Lower indices indicate earlier clones, and the clone ordering on the x-axis is determined by time of maximum contribution, showing emergence of new clones over time. This ordering is shared among time points, enabling comparison of the behavior of individual clones across time. Because contribution is assessed fractionally, the y-axis is from 0 to 1.