Extended Data Fig. 1: Characterization of CRISPR Screen systems.

(a) Comparison of expression profiles of the different readout populations from our screens to lineage specific signatures from 3 different studies, named along the bottom of the graph. Comparisons are based on enrichment analyses between the screen signatures and the reference signatures. Dot colour and size relate to log2 odds ratio and -log10 adjusted p-value, respectively. CLP – Common Lymphoid Progenitor, MkP – Megakaryocyte Progenitor, IMP – Immature Myeloid Progenitor, Ery1-4 – Erythroblasts, Neu1-4 – Neutrophils, Mono1-3 – Monocytes. P-values were calculated using the Fisher’s exact test. (b) Comparison between the expression profiles of FACS-sorted populations from our ex vivo systems and a single-cell map of normal haematopoiesis⁵⁶. Bulk transcriptomic signatures derived from FACS-sorted populations were projected on the single-cell map from Izzo and colleagues. (c) Example distribution of the CF lineage scores calculated from the Cas9 (green border) and Non-Cas9 (grey) populations. (d) Replicate analysis for 200 CFs screened in a second experiment under Self-renewal (top) and Lineage Priming conditions (bottom). (left) heatmaps showing correlation (Spearman) between two replicates, (right) scatter plots showing correlation (Spearman) between replicates. P-values are based on the algorithm AS 89 using the function cor.test in R. (e) Lineage scores for all hits. The color of each dot represents the aggregated lineage score. The size represents the number of significant guides, as per key to the right. All values are shown in Supplementary Table 3.