Fig. 4: Mouse HGG-MYCN reveal a high intratumoral heterogeneity with oligodendroglial and neural cell populations and a time-resolved change in tumor composition.

a UMAP of single cell RNA sequencing data of seven mouse HGG-MYCN (2xP43, 2xP70, 2xP77 and 1x P92) including 24.938 cells. 23 cell clustered were identified by the Seurat algorithm. b To identify tumor cell clusters, expression of human MYCN and Luciferase (FLUC), were plotted. c, d Cell clusters were annotated by analysis of marker gene expression. This revealed immune as well as stromal cell clusters and three main superclusters of tumor cells. Tumor superclusters consist of an oligodendroglial-like, a neuronal-like, and a cluster which was only detected in the most mature mouse tumor. e Cell clusters were compared to a reference atlas of the VZ/SVZ of the mouse by logistic regression. Similarity in gene expression is displayed in red, less similarity in blue. Mouse tumor cell clusters show similarity to precursor cells of the stem cell niche, suggesting a tumor origin in this region. f UMAP and bargraph depiciting the changes in cell composition of samples of different mouse ages. The TME content is reduced in later tumor stages. Early tumors are only OL-like, during tumor development, an NB-like population appears. At P92, a unique tumor cell population is detected, showing neither OL nor NB-like features. AC astrocyte, aNSC adult neural stem cell, DC dendritic cell, EC endothelial cells, EPN ependymal cells, MES mesenchymal, MG microglia, migr. DC migratory dendritc cells, MOL mature oligodendrocyte, mural fibroblasts, pericytes, smooth muscle cells etc., NB neuroblast, OL oligodendrocytic, OPC oligodendrocytic precursor cell, PC pericytes, SMC smooth muscle cells, TAC transit amplifying cell, TME tumor microenvironment, UMAP uniform manifold approximation and projection.