Home > Publications database > ETMR stem-like state and chemo-resistance are supported by perivascular cells at single-cell resolution. > print

001     302265
005     20250629021244.0
024 7 _ |a 10.1038/s41467-025-60442-9
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041 _ _ |a English
082 _ _ |a 500
100 1 _ |a de Faria, Flavia W
|b 0
245 _ _ |a ETMR stem-like state and chemo-resistance are supported by perivascular cells at single-cell resolution.
260 _ _ |a [London]
|c 2025
|b Springer Nature
336 7 _ |a article
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520 _ _ |a Embryonal tumor with multilayered rosettes (ETMR) is a lethal embryonal brain tumor entity. To investigate the intratumoral heterogeneity and cellular communication in the tumor microenvironment (TME), we analyze in this work single-cell RNA sequencing of about 250,000 cells of primary human and murine ETMR, in vitro cultures, and a 3D forebrain organoid model of ETMR, supporting the main findings with immunohistochemistry and spatial transcriptomics of human tumors. We characterize three distinct malignant ETMR subpopulations - RG-like, NProg-like and NB-like - positioned within a putative neurodevelopmental hierarchy. We reveal PDGFRβ+ pericytes as key communication partners in the TME, contributing to stem cell signaling through extracellular matrix-mediated interactions with tumor cells. PDGF signaling is upregulated in chemoresistant RG-like cells in vivo and plays a role in recruiting pericytes to ETMR TME by finalizing a signaling cascade which promotes the differentiation of non-malignant radial glia cells, derived from our 3D model, into pericyte-like cells. Selective PDGFR-inhibition blocked the lineage differentiation into pericytes in vitro and reduced the tumor cell population in vivo. Targeting ETMR-pericyte interactions in the TME presents a promising therapeutic approach.
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650 _ 7 |a Receptor, Platelet-Derived Growth Factor beta
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650 _ 7 |a Platelet-Derived Growth Factor
|2 NLM Chemicals
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Pericytes: metabolism
|2 MeSH
650 _ 2 |a Pericytes: pathology
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Single-Cell Analysis
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Drug Resistance, Neoplasm: genetics
|2 MeSH
650 _ 2 |a Receptor, Platelet-Derived Growth Factor beta: metabolism
|2 MeSH
650 _ 2 |a Receptor, Platelet-Derived Growth Factor beta: genetics
|2 MeSH
650 _ 2 |a Tumor Microenvironment: genetics
|2 MeSH
650 _ 2 |a Signal Transduction
|2 MeSH
650 _ 2 |a Brain Neoplasms: pathology
|2 MeSH
650 _ 2 |a Brain Neoplasms: genetics
|2 MeSH
650 _ 2 |a Brain Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Brain Neoplasms: drug therapy
|2 MeSH
650 _ 2 |a Neoplastic Stem Cells: metabolism
|2 MeSH
650 _ 2 |a Neoplastic Stem Cells: pathology
|2 MeSH
650 _ 2 |a Cell Differentiation
|2 MeSH
650 _ 2 |a Cell Communication
|2 MeSH
650 _ 2 |a Organoids
|2 MeSH
650 _ 2 |a Platelet-Derived Growth Factor: metabolism
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
700 1 _ |a Riedel, Nicole C
|b 1
700 1 _ |a Münter, Daniel
|0 0000-0001-8823-0238
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700 1 _ |a Interlandi, Marta
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700 1 _ |a Göbel, Carolin
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700 1 _ |a Altendorf, Lea
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700 1 _ |a Richter, Mathis
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700 1 _ |a Melcher, Viktoria
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700 1 _ |a Thomas, Christian
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700 1 _ |a Roy, Rajanya
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700 1 _ |a Schoof, Melanie
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700 1 _ |a Bedzhov, Ivan
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700 1 _ |a Moreno, Natalia
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700 1 _ |a Graf, Monika
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700 1 _ |a Hotfilder, Marc
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700 1 _ |a Holdhof, Dörthe
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700 1 _ |a Hartmann, Wolfgang
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700 1 _ |a Bruns, Ann-Katrin
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700 1 _ |a Brentrup, Angela
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700 1 _ |a Liesche-Starnecker, Friederike
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700 1 _ |a Maerkl, Bruno
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700 1 _ |a Sandmann, Sarah
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700 1 _ |a Varghese, Julian
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700 1 _ |a Dugas, Martin
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700 1 _ |a Pinto, Pedro H
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700 1 _ |a Balbach, Sebastian T
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700 1 _ |a Lu, I-Na
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700 1 _ |a Rossig, Claudia
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700 1 _ |a Soehnlein, Oliver
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700 1 _ |a Canak, Aysegül
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700 1 _ |a Ebinger, Martin
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700 1 _ |a Schuhmann, Martin
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700 1 _ |a Schittenhelm, Jens
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700 1 _ |a Frühwald, Michael F
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700 1 _ |a Schüller, Ulrich
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700 1 _ |a Albert, Thomas K
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700 1 _ |a Walter, Carolin
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700 1 _ |a Bruder, Jan M
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700 1 _ |a Kerl, Kornelius
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773 _ _ |a 10.1038/s41467-025-60442-9
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