Fig. 5: COL1A1 is a central hub of oncostream organization and glioma malignancy. | Nature Communications

Fig. 5: COL1A1 is a central hub of oncostream organization and glioma malignancy.

From: Spatiotemporal analysis of glioma heterogeneity reveals COL1A1 as an actionable target to disrupt tumor progression

Fig. 5

A Network analysis of differentially expressed (DE) genes comparing oncostreams vs. no-oncostreams. Node size reflects the degree of connectivity. Clusters of nodes with the same color illustrate modules of highly interacting genes. B Immunofluorescence analysis of COL1A1 expression in GEMM of glioma comparing NPA (IDH1-WT) vs NPAI (IDH1mut). Representative confocal images display COL1A1 expression in green (Alexa 488) and nuclei in blue (DAPI). Scale bar: 50 μm. C Bar graphs represent COL1A1 quantification. NPA n = 5 and NPAI n = 6 tumors for each experimental condition were used for the analysis. Ten fields from each tumor section were selected at random. Graphs present mean ± SEM. Two-sided t-test, **p = 0.0087. D Immunofluorescence analysis of COL1A1 expression in human GBM and LGG tumors. COL1A1 expression in green and nuclei in blue. Scale bar: 50 μm. E Bar graphs represent COL1A1 quantification n = 5 (LGG) and n = 8 (GBM) tumors were used. Ten fields of each section were randomly selected. Graphs present mean ± SEM. Mann–Whitney two-sided t-test, **p = 0.0031. F, G GEMM of glioma with COL1A1 inhibition. F Kaplan–Meier survival curve comparing NPA (MS: 68 days; n: 14) vs NPAshCOL1A1 (MS: 123 days; n = 28). G Kaplan–Meier survival curve comparing NPD (MS: 74 days; n = 15) vs. NPDshCOL1A1 (MS: 98 days; n = 17). Log-rank (Mantel–Cox) test. ****p < 0.0001, **p = 0.0126. H Immunofluorescent COL1A1 expression in NPA and NPD and  Col1a1 downregulation (NPAshCOL1A1 and NPDshCOL1A1); confocal images of COL1A1 expression in green and nuclei in blue. Arrows indicate COL1A1 enriched perivascular cells. Scale bar: 50 μm. I COL1A1 quantification of fluorescence integrated density. Ten fields of each tumor section were selected at random (NPA: n = 5, NPAshCOL1A1: n = 5, NPD; n = 7, NPDshCOL1A1: n = 5). Two-sided t-test, p = 0.0104, ns = not significant. Graphs present mean ± SEM. J Representative Hematoxylin and Eosin images of the histopathological identification of oncostreams comparing COL1A1 knockdown tumors versus controls. Scale bars: 20 μm. K Quantitative analysis of oncostream areas using deep learning analysis (NPA: n = 10, NPAshCOL1A1: n = 10, NPD; n = 12, NPDshCOL1A1: n = 4 samples used per experimental condition). Graphs present mean ± SEM; Two-sided t-test analysis, NPA vs NPAshCOL1A1 *p = 0.0199; NPD vs NPDshCOL1A1 *p = 0.0124.

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