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. Author manuscript; available in PMC: 2020 Mar 18.
Published in final edited form as: Nature. 2019 Sep 18;573(7775):539–545. doi: 10.1038/s41586-019-1563-y

Figure 4: Glioma membrane depolarization promotes glioma progression.

Figure 4:

a, Optogenetic paradigm for glioma depolarization. ChR2-expressing glioma (blue), region of analysis (light blue). b, Proliferation index of SU-DIPGXIII-FL-ChR2 xenograft after mock stimulation (mock stim) or blue light stimulation (stim) measured as percent of GFP+/HNA+ cells expressing Ki67 (mock stim, n=8; stim, n=9 mice). c, As in (b), but SU-DIPGVI-ChR2 xenografts (n=6 mice/group). d, Representative confocal micrographs from (c), illustrating proliferating SU-DIPGVI-ChR2. Red=human nuclei; white=Ki67. Scale bar=50μm. e-f, Kaplan-Meier survival curves of SU-DIPGXIII-P* xenografts overexpressing e, GFP-only (green) or GluA2-WT-GFP (red) and f, GFP-only (in 80% of cells, green) or GluA2-DN-GFP (in 80% of cells, blue); n=5 mice/group. g, Competitive outgrowth of non-GluA2-DN-GFP-expressing cells in (f), determined by GFP/total human nuclei pixel intensity; (n=3 mice/group). h, Representative confocal micrographs of (f-g). White=human nuclei; green=GFP. Scale bar=50μm. i, Representative confocal images of SU-DIPGXIII-FL xenografts expressing GFP-only control (top) or GluA2-DN-GFP (bottom). Gray=MBP; White=glioma-GFP. Scale bar=500μm. j, Quantification of (i) (n=8 mice/group). k, Proliferation index of SU-DIPGVI xenografts treated with perampanel (AMPAR blocker) or vehicle control; (n=8 mice/group). l, Proliferation index of SU-DIPGXIII-FL in mice treated with meclofenamate (gap junction blocker) or vehicle control; (n=9 vehicle, n=8 treated mice). Data shown as mean±s.e.m (b,c,g,j,k,l). **P<0.01. ***P<0.001, ****P<0.0001. P-values determined by two-tailed unpaired Student’s t-test (b,c,g,k,l); two-tailed log rank analyses (e,f); two-sided Mann-Whitney test (j).