Extended Data Fig. 9: Regulation of neuroblastoma by markers of normal adrenal medullary development.
From: Single-cell transcriptomic analyses provide insights into the developmental origins of neuroblastoma
a, Dot plot showing expression of genes with strong enhancers described to engage in enhancer hijacking events in neuroblastoma, in adrenal medullary cell populations. b, Violin plots with normalized expression of adrenal medullary developmental genes in neuroblastoma subgroups. c, Heat map illustrating activity of adrenal medullary transcription factors in neuroblastoma shown as fraction of cells in which the regulon was found active by subgroup. d, UMAP embedding showing single MYCN-amplified IMR5/75 neuroblastoma cells with tetracyclin-inducible shRNAs targeting MYCN and generating MYCN high (-Tet) and MYCN low (+Tet) cells. Cells are colored by levels of regulatable MYCN. e, UMAP visualization of MYCN low and MYCN high cells colored by cell cycle phase. f, Barplot with fractions of cells in each cell cycle phase in MYCN high and MYCN low cells. g, MYCN protein levels in MYCN high and MYCN low IMR5/75 neuroblastoma cells. Detection by western blot using vinculin as loading control. Analysis was performed once on cells from the same experiment as used for single-cell sequencing. h, Violin plots show expression of signatures for Bridge (p < 2.22 × 10−16), con. Progenitor cells (p < 2.22 × 10−16), Chromaffin cells (p = 0.034), late Chromaffin cells (p < 2.22 × 10−16), SCPs (p < 2.22 × 10−16) and late SCPs (p < 2.22 × 10−16) in MYCN-amplified (MYCN high) neuroblastoma cells and MYCN-amplified cells upon MYCN knockdown (MYCN low). Statistical significance was determined by two-sided Wilcoxon rank-sum test.
