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000287645 245__ $$aA clinically applicable connectivity signature for glioblastoma includes the tumor network driver CHI3L1.
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000287645 520__ $$aTumor microtubes (TMs) connect glioma cells to a network with considerable relevance for tumor progression and therapy resistance. However, the determination of TM-interconnectivity in individual tumors is challenging and the impact on patient survival unresolved. Here, we establish a connectivity signature from single-cell RNA-sequenced (scRNA-Seq) xenografted primary glioblastoma (GB) cells using a dye uptake methodology, and validate it with recording of cellular calcium epochs and clinical correlations. Astrocyte-like and mesenchymal-like GB cells have the highest connectivity signature scores in scRNA-sequenced patient-derived xenografts and patient samples. In large GB cohorts, TM-network connectivity correlates with the mesenchymal subtype and dismal patient survival. CHI3L1 gene expression serves as a robust molecular marker of connectivity and functionally influences TM networks. The connectivity signature allows insights into brain tumor biology, provides a proof-of-principle that tumor cell TM-connectivity is relevant for patients' prognosis, and serves as a robust prognostic biomarker.
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000287645 7001_ $$0P:(DE-He78)e50ff195896914d35f54ed1bf913e270$$aHoffmann, Dirk Carsten Frieder$$b1$$eFirst author$$udkfz
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000287645 7001_ $$0P:(DE-HGF)0$$aAzorin, Daniel D$$b3
000287645 7001_ $$0P:(DE-He78)b560411dc6b7b16b688355a5f0cb08f8$$aHausmann, David$$b4$$udkfz
000287645 7001_ $$0P:(DE-He78)07de1c0592124175413da2fb91f61b5a$$aXie, Ruifan$$b5
000287645 7001_ $$aHuppertz, Magnus-Carsten$$b6
000287645 7001_ $$00000-0002-7883-8079$$aHiblot, Julien$$b7
000287645 7001_ $$0P:(DE-He78)8aad075b17d93a5636a34942bdbd7ee6$$aSievers, Philipp$$b8$$udkfz
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000287645 7001_ $$0P:(DE-He78)6f03d3271fd11bb3dc3efca8a16f0cbb$$aCebulla, Gina$$b11$$udkfz
000287645 7001_ $$0P:(DE-He78)6b3b1cf7d9ae5f0e2b6a7d2fbb10fe8e$$aKourtesakis, Alexandros$$b12$$udkfz
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000287645 7001_ $$0P:(DE-He78)ce9cbc0fcc94b04884d88105f812ed01$$aRatliff, Miriam$$b14$$udkfz
000287645 7001_ $$0P:(DE-He78)067cfcfec6965dd012bfdfcbae194579$$aMandelbaum, Henriette$$b15
000287645 7001_ $$0P:(DE-He78)bb545561110f9a827ab21f8586566205$$aJung, Erik$$b16
000287645 7001_ $$aJabali, Ammar$$b17
000287645 7001_ $$aHorschitz, Sandra$$b18
000287645 7001_ $$0P:(DE-He78)bac03ea8237bbc7b1290321d845ddef7$$aErnst, Kati$$b19$$udkfz
000287645 7001_ $$0P:(DE-He78)fa7f7d7870419d5952e598216bf0a2ee$$aReibold, Denise$$b20$$udkfz
000287645 7001_ $$0P:(DE-He78)7b85969869bce221ac5186173255845f$$aWarnken, Uwe$$b21$$udkfz
000287645 7001_ $$0P:(DE-He78)cc84982886796806e5def16a9fa227a1$$aVenkataramani, Varun$$b22$$udkfz
000287645 7001_ $$0P:(DE-He78)18218139eec55d83cf82679934e5cd75$$aWill, Rainer$$b23$$udkfz
000287645 7001_ $$00000-0001-9898-5351$$aSuvà, Mario L$$b24
000287645 7001_ $$aHerold-Mende, Christel$$b25
000287645 7001_ $$0P:(DE-He78)a1f4b408b9155beb2a8f7cba4d04fe88$$aSahm, Felix$$b26$$udkfz
000287645 7001_ $$0P:(DE-He78)6c294453ee36ad59deddc5494fa6aa4b$$aWinkler, Frank$$b27$$udkfz
000287645 7001_ $$0P:(DE-He78)f2a782242acf94a3114d75c45dc75b37$$aSchlesner, Matthias$$b28$$udkfz
000287645 7001_ $$0P:(DE-He78)92e9783ca7025f36ce14e12cd348d2ee$$aWick, Wolfgang$$b29$$udkfz
000287645 7001_ $$0P:(DE-He78)5c2c9cbe6ce72553684d82d94aebdadd$$aKessler, Tobias$$b30$$eLast author$$udkfz
000287645 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-024-45067-8$$gVol. 15, no. 1, p. 968$$n1$$p968$$tNature Communications$$v15$$x2041-1723$$y2024
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