Fig. 3: Patient intra-tumor heterogeneity reflects SA lineage-related transcriptome plasticity.

a UMAP plot of 167,172 NB cells from patient samples colored by unsupervised clustering. Only NB cells were kept for the analysis. b Comparison of transcriptomic states in NB patient single cell data with annotated clusters of NB cells exposed to embryonic microenvironments in the avian model. Similarity score was computed based on Spearman correlation across reference markers. c Heatmap of the scaled expression values for marker genes of human SNPCs/Nbt-like clusters of NB cells exposed to the embryonic microenvironment in NB patient sample transcriptomic clusters. d UMAP plot of NB cells from patient samples colored and labeled by SA lineage-related transcriptome states. e Bar plot of fractions of NB cells assigned to SA-related transcriptomic states per patient sample with associated clinical information. f Heatmap with hierarchical clustering of 649 RNA-seq patient samples from Kocak’s cohort with associated clinical information based on deconvolution, using patient NB scRNA-seq atlas as a reference to assess proportion of NB transcriptomic states. g Kaplan–Meier analysis of EFS in NB patients according to SA lineage-related hierarchical clustering (group1 to 4). Log-rank test with Bonferroni adjustment was performed to compare survival curves. h Forest plot of hazard ratio depending on SA lineage-related NB profiles (group 1 to 4) from Cox regression EFS analyses in multivariable analyses adjusted for age, sex, MYCN status and INSS classification. Error bars represent the 95% confidence interval of the likelihood test performed on the calculated hazard ratio (two-sided test). i–k Kaplan–Meier analysis of EFS in NB patients according to the relative proportion of SNPCs-like (i), comSNPCs-like (j) or Nbts-like states (k). Log-rank test was performed. Error bands show the 95% confidence interval. Source data are provided as a source data file.