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dc.contributor.authorDirkse, Annaen_US
dc.contributor.authorGolebiewska, Annaen_US
dc.contributor.authorBuder, Thomasen_US
dc.contributor.authorNazarov, Petr V.en_US
dc.contributor.authorMuller, Arnauden_US
dc.contributor.authorPoovathingal, Suresh K.en_US
dc.contributor.authorBrons, Nicolaas H. C.en_US
dc.contributor.authorLeite, Soniaen_US
dc.contributor.authorSauvageot, Nicolasen_US
dc.contributor.authorSarkisjan, Dzjemmaen_US
dc.contributor.authorSeyfrid, Mathieuen_US
dc.contributor.authorFritah, Sabrinaen_US
dc.contributor.authorStieber, Danielen_US
dc.contributor.authorMichelucci, Alesandroen_US
dc.contributor.authorHertel, Franken_US
dc.contributor.authorHerold-Mende, Christelen_US
dc.contributor.authorAzuaje, Franciscoen_US
dc.contributor.authorSkupin, Alexanderen_US
dc.contributor.authorBjerkvig, Rolfen_US
dc.contributor.authorDeutsch, Andreasen_US
dc.contributor.authorVoss-Böhme, Anjaen_US
dc.contributor.authorNiclou, Simone Pierretteen_US
dc.PublishedDirkse A, Golebiewska A, Buder T, Nazarov PV, Muller A, et al. Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment. Nature Communications. 2019;10:1787eng
dc.description.abstractThe identity and unique capacity of cancer stem cells (CSC) to drive tumor growth and resistance have been challenged in brain tumors. Here we report that cells expressing CSC-associated cell membrane markers in Glioblastoma (GBM) do not represent a clonal entity defined by distinct functional properties and transcriptomic profiles, but rather a plastic state that most cancer cells can adopt. We show that phenotypic heterogeneity arises from non-hierarchical, reversible state transitions, instructed by the microenvironment and is predictable by mathematical modeling. Although functional stem cell properties were similar in vitro, accelerated reconstitution of heterogeneity provides a growth advantage in vivo, suggesting that tumorigenic potential is linked to intrinsic plasticity rather than CSC multipotency. The capacity of any given cancer cell to reconstitute tumor heterogeneity cautions against therapies targeting CSC-associated membrane epitopes. Instead inherent cancer cell plasticity emerges as a novel relevant target for treatment.en_US
dc.rightsAttribution CC BYeng
dc.titleStem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironmenten_US
dc.typePeer reviewed
dc.typeJournal article
dc.rights.holderCopyright 2019 The Author(s)
dc.source.journalNature Communications

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