Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment [* Cross-Reference *]

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Anne Dirkse; Anna Golebiewska; Thomas Buder; Petr V. Nazarov; Arnaud Muller; Suresh Poovathingal; Nicolaas H. C. Brons; Sónia Leite; Nicolas Sauvageot; Dzjemma Sarkisjan; Mathieu Seyfrid; Sabrina Fritah; Daniel Stieber; Alessandro Michelucci; Frank Hertel; Christel Herold‐Mende; Francisco Azuaje; Alexander Skupin; Rolf Bjerkvig; Andreas Deutsch; Anja Voß-Böhme; Simone P. Niclou, 2026, "Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment [* Cross-Reference *]", https://lore.list.lu/citation?persistentId=perma:LIST.MGHBJO, LIST Open Repository, V1

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Description	The 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. (2019-04-16) *This entry has been automatically imported via OpenAlex by LIST harvest scripts. Please refer to https://doi.org/10.1038/s41467-019-09853-z for the original and latest version of the publication* (2026-07-01)
Subject	Chemistry; Mathematical Sciences; Medicine, Health and Life Sciences; Physics
Keyword	Cancer stem cell, Biology, Tumor microenvironment, Stem cell, Cancer cell, Phenotype, Transcriptome, Glioblastoma, Cancer, Cell biology, Cell, Cancer research, Neuroscience, Tumor cells, Gene, Genetics, Gene expression
License/Data Use Agreement	CC BY 4.0


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Persistent Identifier	perma:LIST.MGHBJO
Publication Date	2026-07-06
Title	Stem cell-associated heterogeneity in Glioblastoma results from intrinsic tumor plasticity shaped by the microenvironment [* Cross-Reference *]
Other Identifier	https://doi.org/10.1038/s41467-019-09853-z OpenAlex ID: https://openalex.org/W2936375023
Author	Anne Dirkse (University of Luxembourg, Luxembourg Institute of Health, Luxembourg Institute of Science and Technology) - ORCID: https://orcid.org/0000-0003-0778-6651 Anna Golebiewska (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-4160-2521 Thomas Buder (HTW Berlin - University of Applied Sciences, Hochschule für Technik und Wirtschaft Dresden – University of Applied Sciences, Technische Universität Dresden) - ORCID: https://orcid.org/0000-0003-4099-1323 Petr V. Nazarov (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0003-3443-0298 Arnaud Muller (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-3841-4722 Suresh Poovathingal (University of Luxembourg) - ORCID: https://orcid.org/0000-0002-3236-2255 Nicolaas H. C. Brons (Luxembourg Institute of Health) Sónia Leite (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-3898-088X Nicolas Sauvageot (Luxembourg Institute of Health) Dzjemma Sarkisjan (Luxembourg Institute of Health) Mathieu Seyfrid (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-0632-8870 Sabrina Fritah (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-7613-1424 Daniel Stieber (Luxembourg Institute of Health) Alessandro Michelucci (University of Luxembourg, Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0003-1230-061X Frank Hertel (Centre Hospitalier de Luxembourg) Christel Herold‐Mende (Heidelberg University) - ORCID: https://orcid.org/0000-0002-1915-745X Francisco Azuaje (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-9207-9072 Alexander Skupin (University of Luxembourg) - ORCID: https://orcid.org/0000-0002-8955-8304 Rolf Bjerkvig (Luxembourg Institute of Health, University of Bergen) - ORCID: https://orcid.org/0000-0002-9622-7263 Andreas Deutsch (Technische Universität Dresden) - ORCID: https://orcid.org/0000-0002-9005-6897 Anja Voß-Böhme (HTW Berlin - University of Applied Sciences, Hochschule für Technik und Wirtschaft Dresden – University of Applied Sciences, Technische Universität Dresden) - ORCID: https://orcid.org/0000-0001-6510-8694 Simone P. Niclou (Luxembourg Institute of Health) - ORCID: https://orcid.org/0000-0002-3417-9534
Point of Contact	Use email button above to contact. LIST QDKM (LIST)
Description	The 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. (2019-04-16) *This entry has been automatically imported via OpenAlex by LIST harvest scripts. Please refer to https://doi.org/10.1038/s41467-019-09853-z for the original and latest version of the publication* (2026-07-01)
Subject	Chemistry; Mathematical Sciences; Medicine, Health and Life Sciences; Physics
Keyword	Cancer stem cell Biology Tumor microenvironment Stem cell Cancer cell Phenotype Transcriptome Glioblastoma Cancer Cell biology Cell Cancer research Neuroscience Tumor cells Gene Genetics Gene expression
Topic Classification	Cancer Cells and Metastasis Mathematical Biology Tumor Growth Single-cell and spatial transcriptomics
Deposit Date	2019-04-16
Data Type	Article
Data Source	Nature Communications

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