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. 2022 Apr 13;24(9):1494–1508. doi: 10.1093/neuonc/noac085

Fig. 3.

Fig. 3

Hierarchical organization of meta-programs uncovers meta-program dynamics in new and recurrent glioblastoma and a bi-progenitor origin. Meta-program UMAP embedding of cancer cells from all (A), new (B), and recurrent (C) patients. Arrows indicate the sample-wise mean RNA velocity of cells within the voxel. Cells are colored according to their highest meta-program score. Cells with a high combined cell cycle meta-program score (>100) are labeled bright red. (D) Bar graph showing the proportion of total and cycling cells expressing a meta-program as the dominant meta-program. The OPC, APC, and the neuronal meta-program are enriched in cycling cells, while others are stable or decreased. (E) Gaussian-filtered expression of the astrocytic, APC, OPC, and oligodendrocytic meta-programs in cells according to their position along UMAP1. (F) Average expression of meta-programs by sample, stratified according to new, early recurrent, and late recurrent glioblastoma. *<0.05. (G) Representative CD44 expression in a paired patient with new and recurrent glioblastoma (scale bar = 50 µm). The boxplots represent the absolute change in the percentage of CD44-positive cells (%CD44+) from new to recurrent tumors in 21 paired new and recurrent patients stratified by recurrence time (early: <12 months; late: >12 months). These boxplots show the first quartile, median, and third quartile with whiskers corresponding to 1.5 times the interquartile range. Most patients with an early recurrence showed an increase in average CD44 fluorescence intensity (P = .007). Two-sample Student’s t test was used. (H) Patient-wise correlation of the velocity origin score to the meta-programs, stratified by new and recurrent samples. The origin score corresponds to the frequency at which a cell is the endpoint of a backward Markov process minus the frequency of being the endpoint of a forward Markov process. A positive correlation indicates cells expressing a meta-program tend toward the origin of the velocity field, while a negative correlation indicates these cells tend toward the terminus. P-values: *<.01; **<.001; ***<.0005. Abbreviations: APC, astrocyte progenitor cell; c.cycle, cell cycle; GSC, glioma stem cell; HK, housekeeping; mes, mesenchymal; neuro, neuronal; oligo, oligodendrocyte; OPC, oligodendrocyte progenitor cell.