Extended Data Fig. 9: Extended analysis of Chromatin Factor roles in Npm1c/Flt3-ITD Leukemia.
From: In vivo screening characterizes chromatin factor functions during normal and malignant hematopoiesis
(a) UMAP showing original projection of Npm1c/Flt3-ITD single-cell transcriptomes. (b) UMAP projection of Npm1c/Flt3-ITD single-cell transcriptomes projected over the Hematopoietic in vivo map derived from bone marrow at 14-day post-transplant. (c) Scaled CITE-seq signal for 9 surface markers in leukemic cells. (d) Expression analysis of markers over the different leukemic clusters. According to their mRNA and Surface marker patterns these are classified into: Leukemic Stem Cells (LSC), GMP-like, Monocyte-like, Granulocyte-like, Basophil-like, Megakaryocyte-like and Erythroid-like. Clusters in red are absent in the unperturbed (NTC) cells. (e) Exemplar sorting strategy of leukemic subpopulations showing traits of differentiation into Granulocyte (Gran) or mixed Erythroid-Basophil populations. (f) Enrichment analyses of all CF-KOs across leukemia subpopulations. Disruption of factors highlighted in red induce differentiation pathways in leukemia. All values are shown in Supplementary Tables 6 and 7. (g). Plot showing the abundance of specific CF-sgRNAs with respect to Control-sgRNAs across the leukemic subclusters. Subclusters deviating from the diagonal are rare or absent in the unperturbed scenario. (h) Growth curves of Prmt1- and Prmt5-KO cells, n=3 biologically independent experiments. The cells expressing each sgRNA harbor a BFP reporter and, the assay measures the change in the proportion of BFP expressing cells over time. ***P<0.001 (Two Way ANOVA). Error bars are SEM.
