Extended Data Fig. 4: B-ALL developmental states within B-ALL samples.

a,b) Validation through projection of human fetal lung data. a) 9,491 single cell transcriptomes mapped to human B cell development from fetal lung tissue profiled in Barnes et al.⁴¹. Projected cells are colored by cell type labels assigned in the original publication. Reference single-cell transcriptomes from our B cell development atlas are depicted in gray. b) Density plots depicting projected single-cell transcriptomes split by each author assigned cell type within the query fetal lung scRNA-seq data. Darker shades of red depict higher density of query cells within a given region along the reference atlas. c) UMAP embedding based on cell state composition from 89 B-ALL samples. Color scheme depicts centered log ratio (CLR) normalized abundance of each mapped cell population for each sample. d) Consolidation of similar B-ALL cell states into broader developmental states. To identify B-ALL states with correlated abundance across patient samples, NMF was performed on the normalized abundance scores of all mapped cell states from B-ALL bone marrow samples and NMF modules were interpreted based on the weights assigned to the cell states that comprise each module. e) For NMF modules that correspond to a distinct stage along B-lymphoid development, termed ‘Developmental State’, feature weights are visualized in this heatmap by constituent cell type. f) Abundance of broad developmental states defined by NMF spanning early myeloid progenitors and plasmacytoid DC cells. Color scheme denotes scaled abundance (CLR) of each indicated population. g) Remaining genomic subtypes (DUX4-R, BCR::ABL1-like (CRLF2-R), BCR::ABL1-like (non-CRLF2-R), iAMP21, PAX5alt and near haploid) are overlaid based on the cell composition of their constituent patient samples. h,i) Developmental state in ETV6::RUNX1 B-ALL. h) Cell state composition-based clustering of 8 ETV6::RUNX1 B-ALL samples from Mehtonen et al.⁴⁴ and 7 ETV6::RUNX1-like B-ALL samples from this study. Each column represents a scRNA-seq sample. i) Projection results on the B cell development map of ETV6::RUNX1 B-ALL samples from Mehtonen et al.⁴⁴.