Fig. 6: CDH2 and PTPRZ1 drive meningioma cell proliferation and tumorigenesis.
a qRT-PCR assessment of CDH2 and PTPRZ1 expression in M10GdCas9-KRAB meningioma cells after transduction of sgRNAs targeting these genes demonstrates repression of each gene relative to cells transduced with non-targeted control sgRNAs (sgNTC). b, c Immunofluorescence of Ki-67 (green) in M10GdCas9-KRAB meningioma cells after transduction sgRNAs shows that repression of CDH2 and PTPRZ1 blocks meningioma cell proliferation. DNA is marked with Hoeschst (blue). Scale bar, 100 μm. d Treatment of M10G cells with the CDH2 antagonist ADH-1 0.2 mg/ml for 48 h blocks meningioma cell proliferation. e Live confocal microscopy of M10GdCas9-KRAB meningioma cells in coculture with human cerebral organoids demonstrates that transduction of sgCDH2 blocks meningioma tumorigenesis compared to transduction of sgNTC. f, g Quantification of M10GdCas9-KRAB (red) intensity in coculture with human cerebral organoids (green) after 10 days shows that transduction of sgCDH2 and treatment with ADH-1 0.2 mg/ml blocks meningioma tumorigenesis. Scale bar, 100 μm. h Immunofluorescence of Ki67 in M10G, BenMen, and MSC1 meningioma cells shows that pharmacologic inhibition of CDH2 with ADH-1 0.2 mg/ml blocks meningioma cell proliferation. i Quantification of BenMen, MSC1, and MSC5 intensity in coculture with human cerebral organoids after 10 days shows that treatment with ADH-1 0.2 mg/ml blocks meningioma tumorigenesis. *P ≤ 0.05, two-tailed Student’s unpaired t test. Mean ± standard error of the mean (as shown by error bars in a, b, d, g, h, and i) are denoted.
