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. 2020 Sep 23;11:4803. doi: 10.1038/s41467-020-18582-7

Fig. 5. CDH2 and PTPRZ1 underlie meningioma tumorigenesis in coculture with human cerebral organoids.

Fig. 5

a Confocal microscopy of M10G WHO grade I and M13C WHO grade III meningioma cells labeled with red fluorescent protein in 2D culture. Scale bar, 100 μm. b Confocal microscopy reveals that M10G and M13C meningioma cells form tumor spheres in 3D culture. Scale bar, 100 μm. c Live confocal microscopy of meningioma cells (red) in 3D coculture with human cerebral organoids (green) for 30 h demonstrates that M10G cells form tumor spheres adjacent to organoids and M13C cells form tumor spheres that invade organoids. Scale bar, 200 μm. d Integrated single cell RNA sequencing analysis of WHO Grade III meningioma cell 2D culture, 12-h and 14-day 3D cultures, 14-day cerebral organoid only culture, and 12-h and 14-day 3D cocultures with cerebral organoids plotted in UMAP space and shaded by sample reveals distinct clusters segregating primarily by sample. e UMAP of 2D meningioma cells demonstrates five clusters distinguished by enrichment of extracellular matrix organization and integrin interaction genes (C0), cell proliferation and FOXM1 target genes (C1), metabolism (C2), and a rare subpopulation marked by expression of the ADC high genes CDH2 and PTPRZ1 (C4). f UMAP of 3D meningioma cells at 12 h and g at 14 days reveals persistence of extracellular matrix organization and proliferating meningioma cells, but loss of meningioma cells expressing ADC high genes CDH2 and PTPRZ1. h UMAP of meningioma cells in co-culture with human cerebral organoids at 12 h and i 14 days demonstrates expression of CDH2 and PTPRZ1 in both cell populations, which increasing expression of as PTPRZ1 over time, as illustrated in feature plots at j 12 h and k 14 days.