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. Author manuscript; available in PMC: 2022 Oct 11.
Published in final edited form as: Nat Cancer. 2022 Apr 14;3(5):629–648. doi: 10.1038/s43018-022-00348-3

Fig. 8 |. MAT2A depletion or MR impedes DIPG growth in vivo.

Fig. 8 |

a, Kaplan–Meier survival curve showing that MR increases survival of the H3K27MPP DMG model. Kaplan–Meier survival curve of H3K27MPP cells injected into the midbrain-pons of immunocompetent C57BL/6 mice. A log-rank Mantel–Cox test was performed between the groups with n = 7 mice per group (4 male and 3 female). ***P = 0.0003. A post hoc power estimation based on the sample size with a two-sided α of 0.05 provided a >0.99 power. b, H&E and Ki67 staining confirming high-grade glioma histology from H3K27MPP-injected mice. c, Ki67 quantification confirming loss of Ki67-positive cells from H3K27MPP tumors on low-methionine diet compared to control chow. Ki67 indices were calculated from three animals per group with each index being an average of five high-magnification field of views (control versus low-methionine diet **P = 0.003). d, Quantification of SAM concentrations in H3K27MPP tumors on a low-methionine diet compared to control chow (n = 3 tumors per group; control versus low-methionine diet **P = 0.0062). e. Western blotting of MAT2A, OLIG2, H3K36me3 and LAMIN in H3K27MPP tumors from control and low-methionine diets. f, Quantification of MAT2A and OLIG2 normalized to β-actin and H3K36me3 normalized to LAMIN from e from three independent western blots comparing H3K27MPP tumors on control diet versus a low-methionine diet (control versus MR MAT2A ***P = 0.000955; OLIG2 ***P = 0.000236; and H3K36me3 ***P = 0.000118). g, In vivo orthotopic DIPG13p xenograft with control, MAT2A knockdown (+ dox) or DIPG13p xenografts put on a low-methionine data. A log-rank Mantel–Cox test was performed between the groups with n = 5 mice per group (5 female) (control versus MAT2A knockdown **P = 0.0019) and (control versus low-methionine diet **P = 0.0019). A post hoc power estimation based on the sample size with a two-sided α of 0.05 provided: control versus MAT2A knockdown 0.995 power and control versus low methionine, 0.991 power. h. H&E and MAT2A immunohistochemistry (IHC). I. Proposed model of compromised MAT2A function in DIPG compared to healthy cells. Statistical analysis was performed using a two-tailed, unpaired t-test (c,d,f). Data are displayed as mean ± s.e.m.