{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T01:15:58Z","timestamp":1789953358133,"version":"4.0.1"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T00:00:00Z","timestamp":1506297600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Berliner Krebsgesellschaft","award":["EUFF-2012-36"],"award-info":[{"award-number":["EUFF-2012-36"]}]},{"DOI":"10.13039\/501100006188","name":"Einstein Stiftung Berlin","doi-asserted-by":"publisher","award":["EZK-2012-157"],"award-info":[{"award-number":["EZK-2012-157"]}],"id":[{"id":"10.13039\/501100006188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0185376","type":"journal-article","created":{"date-parts":[[2017,9,25]],"date-time":"2017-09-25T15:10:33Z","timestamp":1506352233000},"page":"e0185376","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["Cellular heterogeneity contributes to subtype-specific expression of ZEB1 in human glioblastoma"],"prefix":"10.1371","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9138-805X","authenticated-orcid":true,"given":"Philipp","family":"Euskirchen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josefine","family":"Radke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S\u00f6ren","family":"Schmidt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Schulze Heuling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Kadikowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meron","family":"Maricos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Knab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Grittner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norman","family":"Zerbe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus","family":"Czabanka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Dieterich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hrvoje","family":"Miletic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sverre","family":"M\u00f8rk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arend","family":"Koch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Endres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Harms","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2017,9,25]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma","volume":"352","author":"R Stupp","year":"2005","journal-title":"New England Journal of Medicine"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2009.11.007","article-title":"Epithelial-Mesenchymal Transitions in Development and Disease","volume":"139","author":"JP Thiery","year":"2009","journal-title":"Cell"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1038\/ncb1998","article-title":"The EMT-activator ZEB1 promotes tumorigenicity by repressing stemness-inhibiting microRNAs","volume":"11","author":"U Wellner","year":"2009","journal-title":"Nat Cell Biol"},{"key":"ref4","article-title":"ATM-mediated stabilization of ZEB1 promotes DNA damage response and radioresistance through CHK1","author":"P Zhang","year":"2014","journal-title":"Nat Cell Biol"},{"key":"ref5","doi-asserted-by":"crossref","DOI":"10.1038\/ncomms6241","article-title":"Metastasis is regulated via microRNA-200\/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression","volume":"5","author":"L Chen","year":"2014","journal-title":"Nat Commun"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"e1443","DOI":"10.1038\/cddis.2014.395","article-title":"TGF-\u03b2 is an inducer of ZEB1-dependent mesenchymal transdifferentiation in glioblastoma that is associated with tumor invasion","volume":"5","author":"JV Joseph","year":"2014","journal-title":"Cell Death Dis"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.canlet.2015.01.010","article-title":"Hypoxia enhances migration and invasion in glioblastoma by promoting a mesenchymal shift mediated by the HIF1\u03b1-ZEB1 axis","volume":"359","author":"JV Joseph","year":"2015","journal-title":"Cancer Lett"},{"key":"ref8","article-title":"ZEB1 Promotes invasion in human fetal neural stem cells and hypoxic glioma neurospheres","author":"U Kahlert","year":"2014","journal-title":"Brain Pathol"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1002\/emmm.201302827","article-title":"The ZEB1 pathway links glioblastoma initiation, invasion and chemoresistance","volume":"5","author":"FA Siebzehnrubl","year":"2013","journal-title":"EMBO Mol Med"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.celrep.2016.12.064","article-title":"Oncogenes Activate an Autonomous Transcriptional Regulatory Circuit That Drives Glioblastoma","volume":"18","author":"DK Singh","year":"2017","journal-title":"Cell Reports"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1007\/s00401-013-1101-1","article-title":"EGFR wild-type amplification and activation promote invasion and development of glioblastoma independent of angiogenesis","volume":"125","author":"KM Talasila","year":"2013","journal-title":"Acta Neuropathol"},{"key":"ref12","article-title":"Prognostic Relevance of Tumor Purity and TERT Promoter Mutations on MGMT Promoter Methylation in Glioblastoma","author":"ES Heuling","year":"2017","journal-title":"Mol Cancer Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.ccr.2006.03.030","article-title":"Tumor stem cells derived from glioblastomas cultured in bFGF and EGF more closely mirror the phenotype and genotype of primary tumors than do serum-cultured cell lines","volume":"9","author":"J Lee","year":"2006","journal-title":"Cancer Cell"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1016\/j.stem.2009.03.014","article-title":"Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens","volume":"4","author":"SM Pollard","year":"2009","journal-title":"Cell Stem Cell"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"M Uhl\u00e9n","year":"2015","journal-title":"Science"},{"issue":"Suppl 1","key":"ref16","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1186\/1746-1596-6-S1-S16","article-title":"Distributed computing in image analysis using open source frameworks and application to image sharpness assessment of histological whole slide images","volume":"6","author":"N Zerbe","year":"2011","journal-title":"Diagn Pathol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"R100","DOI":"10.1186\/gb-2006-7-10-r100","article-title":"CellProfiler: image analysis software for identifying and quantifying cell phenotypes","volume":"7","author":"AE Carpenter","year":"2006","journal-title":"Genome Biology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"R56","DOI":"10.1186\/bcr2615","article-title":"ImmunoRatio: a publicly available web application for quantitative image analysis of estrogen receptor (ER), progesterone receptor (PR), and Ki-67","volume":"12","author":"VJ Tuominen","year":"2010","journal-title":"Breast Cancer Research"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1093\/bioinformatics\/btp120","article-title":"TopHat: discovering splice junctions with RNA-Seq","volume":"25","author":"C Trapnell","year":"2009","journal-title":"Bioinformatics"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1038\/nbt.1621","article-title":"Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation","volume":"28","author":"C Trapnell","year":"2010","journal-title":"Nat Biotechnol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.ccr.2009.12.020","article-title":"Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1","volume":"17","author":"RGW Verhaak","year":"2010","journal-title":"Cancer Cell"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/ng0506-500","article-title":"GenePattern 2.0","volume":"38","author":"M Reich","year":"2006","journal-title":"Nat Genet"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1038\/nature08460","article-title":"Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1","volume":"462","author":"DA Barbie","year":"2009","journal-title":"Nature"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"20828","DOI":"10.1073\/pnas.1008301107","article-title":"miR-200 family and targets, ZEB1 and ZEB2, modulate uterine quiescence and contractility during pregnancy and labor","volume":"107","author":"NE Renthal","year":"2010","journal-title":"PNAS"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2864","DOI":"10.1016\/j.yexcr.2011.09.002","article-title":"NUMB does not impair growth and differentiation status of experimental gliomas","volume":"317","author":"P Euskirchen","year":"2011","journal-title":"Exp Cell Res"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"RESEARCH0034","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"J Vandesompele","year":"2002","journal-title":"Genome Biol"},{"key":"ref27","unstructured":"Bates D, M\u00e4chler M, Bolker B, Walker S. Fitting Linear Mixed-Effects Models using lme4. arXiv:14065823 [stat]. 2014; Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/arxiv.org\/abs\/1406.5823\" xlink:type=\"simple\">http:\/\/arxiv.org\/abs\/1406.5823<\/ext-link>"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.cell.2013.09.034","article-title":"The Somatic Genomic Landscape of Glioblastoma","volume":"155","author":"CW Brennan","year":"2013","journal-title":"Cell"},{"key":"ref29","first-page":"1","article-title":"The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary","author":"DN Louis","year":"2016","journal-title":"Acta Neuropathol"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/neuonc\/now247","article-title":"GlioVis data portal for visualization and analysis of brain tumor expression datasets","volume":"19","author":"RL Bowman","year":"2017","journal-title":"Neuro-oncology"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1016\/j.ccr.2010.03.017","article-title":"Identification of a CpG island methylator phenotype that defines a distinct subgroup of glioma","volume":"17","author":"H Noushmehr","year":"2010","journal-title":"Cancer Cell"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1369\/jhc.2007.950170","article-title":"Multiple immunoenzyme staining: methods and visualizations for the observation with spectral imaging","volume":"56","author":"CM van der Loos","year":"2008","journal-title":"J Histochem Cytochem"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1002\/glia.21136","article-title":"The brain tumor microenvironment","volume":"59","author":"NA Charles","year":"2011","journal-title":"Glia"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"9065","DOI":"10.1158\/0008-5472.CAN-09-2307","article-title":"Intrinsic gene expression profiles of gliomas are a better predictor of survival than histology","volume":"69","author":"LAM Gravendeel","year":"2009","journal-title":"Cancer Res"},{"key":"ref35","article-title":"Activation of canonical WNT\/\u03b2-catenin signaling enhances in vitro motility of glioblastoma cells by activation of ZEB1 and other activators of epithelial-to-mesenchymal transition","author":"U Kahlert","year":"2012","journal-title":"Cancer letters"},{"key":"ref36","article-title":"Post-translational Modifications of OLIG2 Regulate Glioma Invasion through the TGF-\u03b2 Pathway","author":"SK Singh","year":"2016","journal-title":"Cell Rep"},{"key":"ref37","article-title":"SHP-2-upregulated ZEB1 is important for PDGFR\u03b1-driven glioma epithelial-mesenchymal transition and invasion in mice and humans","author":"L Zhang","year":"2016","journal-title":"Oncogene"},{"key":"ref38","article-title":"ZEB1 expression is increased in IDH1-mutant lower-grade gliomas","author":"CL Nesvick","year":"2016","journal-title":"J Neurooncol"},{"key":"ref39","article-title":"Twist predicts poor outcome of patients with astrocytic glioma","author":"K Nordfors","year":"2015","journal-title":"J Clin Pathol"},{"key":"ref40","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.85841","article-title":"Glioblastoma-infiltrated innate immune cells resemble M0 macrophage phenotype","volume":"1","author":"K Gabrusiewicz","year":"2016","journal-title":"JCI Insight"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s004010000286","article-title":"Increased microglia proliferation separates pilocytic astrocytomas from diffuse astrocytomas: a double labeling study","volume":"101","author":"R Klein","year":"2001","journal-title":"Acta Neuropathol"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1002\/path.2370","article-title":"Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas","volume":"216","author":"Y Komohara","year":"2008","journal-title":"J Pathol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"305","DOI":"10.3171\/jns.1979.50.3.0305","article-title":"Macrophages in experimental and human brain tumors. Part 2: studies of the macrophage content of human brain tumors","volume":"50","author":"RA Morantz","year":"1979","journal-title":"J Neurosurg"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1007\/BF00688191","article-title":"Immunohistological study of mononuclear cell infiltrate in malignant gliomas","volume":"74","author":"ML Rossi","year":"1987","journal-title":"Acta Neuropathol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"e43339","DOI":"10.1371\/journal.pone.0043339","article-title":"Increased Microglia\/Macrophage Gene Expression in a Subset of Adult and Pediatric Astrocytomas","volume":"7","author":"JR Engler","year":"2012","journal-title":"PLoS ONE"},{"key":"ref46","article-title":"Correlation of immune phenotype with IDH mutation in diffuse glioma","author":"AS Berghoff","year":"2017","journal-title":"Neuro-oncology"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1101\/gad.294991.116","article-title":"Mutant IDH1 regulates the tumor-associated immune system in gliomas","volume":"31","author":"NM Amankulor","year":"2017","journal-title":"Genes Dev"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1172\/JCI90644","article-title":"Isocitrate dehydrogenase mutations suppress STAT1 and CD8<sup>+<\/sup> T cell accumulation in gliomas","volume":"127","author":"G Kohanbash","year":"2017","journal-title":"J Clin Invest"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0185376","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,18]],"date-time":"2020-10-18T02:44:58Z","timestamp":1602989098000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0185376"}},"subtitle":[],"editor":[{"given":"Ilya","family":"Ulasov","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2017,9,25]]},"references-count":48,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2017,9,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0185376","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,25]]}}}