Fig. 1: scMultiome-sequencing of matched primary and recurrent medulloblastoma.
A Schematic representation of matched primary and recurrent tumor processing for scMultiome. Created in BioRender. Vibhakar, R. (2025) https://BioRender.com/5s3qjvg. Joint Uniform Manifold and Projection (UMAPs) were generated using principal component analysis (PCA) dimensional reduction for gene expression and Latent Semantic Indexing (LSI) indexing for DNA accessibility. (Below) UMAP visualization of snRNAseq data from patient primary (n = 3) and recurrent tumor samples (n = 3). Coloring based on clustering. (Above) UMAP visualization of integrated snATAC and snRNA-seq datasets. Color designates primary cells (pink) and recurrent cells (turquoise). Total nuclei count=50,184. B Cell state designation of 20 clusters based on FindClusters. Non-malignant, diploid cells are circled. C Merged cell states of 12 major clusters. D snGene expression marker dot plot from patient primary (n = 3) and recurrent tumor samples (n = 3). Color indicates average expression and dot size refers to the percentage of cells within the cluster expressing the gene. E Cell proportions in 12 major clusters and 20 minor clusters. Colored by cell type. Violin plot of cell proportions of CNP and Progenitor-Photoreceptor in primary and recurrent tumors. F Xenium in situ spatial transcriptomic analysis of patient primary (n = 2) and recurrent (n = 2) Group 3 tumor. Subpopulations segmented based on gene expression signatures from14. A-Mitotic (MKI67, TOP2A, CENPF, red), B-Progenitor (UQCRB, FOXF2, blue), C1-Differeniated (LUC7L3, PNISR, green), C2-Photoreceptor (NRL, IMPG2, white). H&E staining post Xenium workflow. Scale bar=2 mm. Quantification of subpopulations = % of neoplastic. G fGSEA dot plot of top 10 enriched paths in primary (n = 3) and recurrent tumor (n = 3) populations. The statistical significance of the enrichment score is reported as -Log10(Pval) and the normalized enrichment score (dot size), is also shown. Enrichment score calculations are based on permutation tests. H Representative UMAP marker gene expression from progenitor-photoreceptor cell state, cycling neural progenitor cell state, and Interneuron/Neuron cell state. Total nuclei count=50,184. snMultiome data from patient primary (n = 3) and recurrent tumor samples (n = 3). See also Supplementary Figs. 1–3.
