Key molecular characteristics of MB can be aligned to human fetal cerebellar developmental niches
(A) Schema showing the RL to eCN/UBC developmental branch, the relationship between pseudotime and G3/G4 score, and the staging of key tumor characteristics. From top to bottom: a violin plot showing pseudotime distribution of cells by time of sampling; color transition red to purple marks the point along the developmental trajectory at which cells are defined as eCN/UBC. A fitted sigmoid curve showing the relationship between pseudotime and G3/G4 score. Tumor characteristics are transformed from the G3/G4 scale to the pseudotime scale and marked at the appropriate points. Color bars represent subgroups. Methylation subtypes (I–VIII), mutations, and copy-number changes are marked by box and whisker. Dot represents median distribution; thick line represents the interquartile range; and the thinner lines correspond to range. Dotted horizontal lines denote where the range extends up to a G3/G4 score of 0 and 1 (i.e., matching the ne plus ultra pseudotime after which G3/G4 score is unchanged and exact relationship must be extrapolated). Dotted vertical lines denote the boundaries between highG4, lowG4, G3.5, lowG3, and highG3 (these categories are arbitrary divisions of the continuum for the purposes of visualization and comparison and do not represent “real” subgroups).
(B) Schematic showing the GCP to GN developmental branch and the relationship between pseudotime and MBSHH-Infant or MBSHH-Child metagene. From top to bottom: a violin plot showing pseudotime distribution of cells by time of sample; color transition green to blue marks the point along the developmental trajectory where cells become defined as GN. A loess curve shows the relationship between pseudotime and MBSHH-Infant (red) or MBSHH-Child metagene (dark red). Color bars show parts of trajectory paralleled by MBSHH-Infant or MBSHH-Child tumors.
(C) UMAP of developmental trajectory marked with colors to denote parts most associated with each MB subgroup and the relevant pseudotime (PsT) scale.