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000302265 1001_ $$ade Faria, Flavia W$$b0
000302265 245__ $$aETMR stem-like state and chemo-resistance are supported by perivascular cells at single-cell resolution.
000302265 260__ $$a[London]$$bSpringer Nature$$c2025
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000302265 520__ $$aEmbryonal tumor with multilayered rosettes (ETMR) is a lethal embryonal brain tumor entity. To investigate the intratumoral heterogeneity and cellular communication in the tumor microenvironment (TME), we analyze in this work single-cell RNA sequencing of about 250,000 cells of primary human and murine ETMR, in vitro cultures, and a 3D forebrain organoid model of ETMR, supporting the main findings with immunohistochemistry and spatial transcriptomics of human tumors. We characterize three distinct malignant ETMR subpopulations - RG-like, NProg-like and NB-like - positioned within a putative neurodevelopmental hierarchy. We reveal PDGFRβ+ pericytes as key communication partners in the TME, contributing to stem cell signaling through extracellular matrix-mediated interactions with tumor cells. PDGF signaling is upregulated in chemoresistant RG-like cells in vivo and plays a role in recruiting pericytes to ETMR TME by finalizing a signaling cascade which promotes the differentiation of non-malignant radial glia cells, derived from our 3D model, into pericyte-like cells. Selective PDGFR-inhibition blocked the lineage differentiation into pericytes in vitro and reduced the tumor cell population in vivo. Targeting ETMR-pericyte interactions in the TME presents a promising therapeutic approach.
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000302265 650_7 $$0EC 2.7.10.1$$2NLM Chemicals$$aReceptor, Platelet-Derived Growth Factor beta
000302265 650_7 $$2NLM Chemicals$$aPlatelet-Derived Growth Factor
000302265 650_2 $$2MeSH$$aHumans
000302265 650_2 $$2MeSH$$aPericytes: metabolism
000302265 650_2 $$2MeSH$$aPericytes: pathology
000302265 650_2 $$2MeSH$$aAnimals
000302265 650_2 $$2MeSH$$aSingle-Cell Analysis
000302265 650_2 $$2MeSH$$aMice
000302265 650_2 $$2MeSH$$aDrug Resistance, Neoplasm: genetics
000302265 650_2 $$2MeSH$$aReceptor, Platelet-Derived Growth Factor beta: metabolism
000302265 650_2 $$2MeSH$$aReceptor, Platelet-Derived Growth Factor beta: genetics
000302265 650_2 $$2MeSH$$aTumor Microenvironment: genetics
000302265 650_2 $$2MeSH$$aSignal Transduction
000302265 650_2 $$2MeSH$$aBrain Neoplasms: pathology
000302265 650_2 $$2MeSH$$aBrain Neoplasms: genetics
000302265 650_2 $$2MeSH$$aBrain Neoplasms: metabolism
000302265 650_2 $$2MeSH$$aBrain Neoplasms: drug therapy
000302265 650_2 $$2MeSH$$aNeoplastic Stem Cells: metabolism
000302265 650_2 $$2MeSH$$aNeoplastic Stem Cells: pathology
000302265 650_2 $$2MeSH$$aCell Differentiation
000302265 650_2 $$2MeSH$$aCell Communication
000302265 650_2 $$2MeSH$$aOrganoids
000302265 650_2 $$2MeSH$$aPlatelet-Derived Growth Factor: metabolism
000302265 650_2 $$2MeSH$$aCell Line, Tumor
000302265 7001_ $$aRiedel, Nicole C$$b1
000302265 7001_ $$00000-0001-8823-0238$$aMünter, Daniel$$b2
000302265 7001_ $$aInterlandi, Marta$$b3
000302265 7001_ $$00000-0002-7345-2089$$aGöbel, Carolin$$b4
000302265 7001_ $$aAltendorf, Lea$$b5
000302265 7001_ $$00000-0002-3110-6137$$aRichter, Mathis$$b6
000302265 7001_ $$aMelcher, Viktoria$$b7
000302265 7001_ $$00000-0002-6642-7774$$aThomas, Christian$$b8
000302265 7001_ $$aRoy, Rajanya$$b9
000302265 7001_ $$00000-0002-1373-8130$$aSchoof, Melanie$$b10
000302265 7001_ $$00000-0002-2122-6485$$aBedzhov, Ivan$$b11
000302265 7001_ $$aMoreno, Natalia$$b12
000302265 7001_ $$aGraf, Monika$$b13
000302265 7001_ $$aHotfilder, Marc$$b14
000302265 7001_ $$00000-0003-4664-3848$$aHoldhof, Dörthe$$b15
000302265 7001_ $$aHartmann, Wolfgang$$b16
000302265 7001_ $$aBruns, Ann-Katrin$$b17
000302265 7001_ $$aBrentrup, Angela$$b18
000302265 7001_ $$aLiesche-Starnecker, Friederike$$b19
000302265 7001_ $$aMaerkl, Bruno$$b20
000302265 7001_ $$aSandmann, Sarah$$b21
000302265 7001_ $$00000-0002-7206-3719$$aVarghese, Julian$$b22
000302265 7001_ $$00000-0001-9740-0788$$aDugas, Martin$$b23
000302265 7001_ $$aPinto, Pedro H$$b24
000302265 7001_ $$00000-0003-0212-5758$$aBalbach, Sebastian T$$b25
000302265 7001_ $$aLu, I-Na$$b26
000302265 7001_ $$aRossig, Claudia$$b27
000302265 7001_ $$00000-0002-7854-0694$$aSoehnlein, Oliver$$b28
000302265 7001_ $$0P:(DE-HGF)0$$aCanak, Aysegül$$b29
000302265 7001_ $$00000-0002-4229-8058$$aEbinger, Martin$$b30
000302265 7001_ $$00000-0001-9843-7486$$aSchuhmann, Martin$$b31
000302265 7001_ $$00000-0002-9168-6209$$aSchittenhelm, Jens$$b32
000302265 7001_ $$00000-0002-8237-1854$$aFrühwald, Michael F$$b33
000302265 7001_ $$00000-0002-8731-1121$$aSchüller, Ulrich$$b34
000302265 7001_ $$00000-0002-2488-0706$$aAlbert, Thomas K$$b35
000302265 7001_ $$aWalter, Carolin$$b36
000302265 7001_ $$aBruder, Jan M$$b37
000302265 7001_ $$00000-0002-5676-8102$$aKerl, Kornelius$$b38
000302265 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-025-60442-9$$gVol. 16, no. 1, p. 5394$$n1$$p5394$$tNature Communications$$v16$$x2041-1723$$y2025
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