Figure 6.

Genomic features of human normal cerebella and MBs projected into mouse genomic cerebellar development space. (A) Mouse and human samples in the genomic PC1 (60.15% genomic variance) and PC3 (6.97% genomic variance) of mouse cerebellar development P1-P60. Reference circles mark mouse cerebellum developmental stages. Projected human samples into this mouse genomic space are marked ×: (green) normal cerebella (n = 4); (dark magenta) nonmetastatic (M0) dMB (n = 7); (light magenta) metastatic (M+) dMB (n = 2); (blue) M0 cMB (n = 14); (light blue) M+ cMB (n = 8). Note the configurations of human samples (×) in relation to the mouse stages (○). (B) A stacked histogram of the mouse cerebellum developmental stage/day most closely associated with each human case. Note the higher concentration of M+ MBs with P5 association. Detailed quantitation/distances are shown (C,D; Supplementary Table 5). (C) The average Euclidean distance between each mouse cerebellum development stage to nonmetastatic dMB (n = 7, solid dark-magenta line), metastatic dMB (n = 2, solid light-magenta line), and normal human cerebellum (n = 4, solid green line). Color-matched dotted lines mark the one standard deviation envelope around the average distance. The first 20 genomic mouse PCs are used for calculating distances between human and mouse, which account for 100% of total mouse genomic variance. Note that on average, dMBs (M0 and M+) are closest to the early-developing mouse cerebellum around P5 than to normal human cerebella. The latter are, on average, closest to the late development stages of mouse cerebellum P30-P60 than dMBs. (D) Similar to B, but for cMBs: nonmetastatic cMB (n = 14, solid blue line), metastatic cMB (n = 8, solid light-blue line), and normal human cerebellum (n = 4, solid green line). Again, we note that on average, cMBs (especially M+ cases) are closest to the early-developing mouse cerebellum around P5 than to normal human cerebella. M0 cMBs are closest to P5-P7.