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000179252 1001_ $$aGraf, Monika$$b0
000179252 245__ $$aSingle-cell transcriptomics identifies potential cells of origin of MYC rhabdoid tumors.
000179252 260__ $$a[London]$$bNature Publishing Group UK$$c2022
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000179252 520__ $$aRhabdoid tumors (RT) are rare and highly aggressive pediatric neoplasms. Their epigenetically-driven intertumoral heterogeneity is well described; however, the cellular origin of RT remains an enigma. Here, we establish and characterize different genetically engineered mouse models driven under the control of distinct promoters and being active in early progenitor cell types with diverse embryonic onsets. From all models only Sox2-positive progenitor cells give rise to murine RT. Using single-cell analyses, we identify distinct cells of origin for the SHH and MYC subgroups of RT, rooting in early stages of embryogenesis. Intra- and extracranial MYC tumors harbor common genetic programs and potentially originate from fetal primordial germ cells (PGCs). Using PGC specific Smarcb1 knockout mouse models we validate that MYC RT originate from these progenitor cells. We uncover an epigenetic imbalance in MYC tumors compared to PGCs being sustained by epigenetically-driven subpopulations. Importantly, treatments with the DNA demethylating agent decitabine successfully impair tumor growth in vitro and in vivo. In summary, our work sheds light on the origin of RT and supports the clinical relevance of DNA methyltransferase inhibitors against this disease.
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000179252 7001_ $$00000-0002-6863-2552$$aInterlandi, Marta$$b1
000179252 7001_ $$aMoreno, Natalia$$b2
000179252 7001_ $$00000-0003-4664-3848$$aHoldhof, Dörthe$$b3
000179252 7001_ $$00000-0002-7345-2089$$aGöbel, Carolin$$b4
000179252 7001_ $$aMelcher, Viktoria$$b5
000179252 7001_ $$aMertins, Julius$$b6
000179252 7001_ $$aAlbert, Thomas K$$b7
000179252 7001_ $$aKastrati, Dennis$$b8
000179252 7001_ $$aAlfert, Amelie$$b9
000179252 7001_ $$aHolsten, Till$$b10
000179252 7001_ $$ade Faria, Flavia$$b11
000179252 7001_ $$aMeisterernst, Michael$$b12
000179252 7001_ $$aRossig, Claudia$$b13
000179252 7001_ $$aWarmuth-Metz, Monika$$b14
000179252 7001_ $$00000-0002-3595-8951$$aNowak, Johannes$$b15
000179252 7001_ $$00000-0002-4341-4719$$aMeyer Zu Hörste, Gerd$$b16
000179252 7001_ $$aMayère, Chloe$$b17
000179252 7001_ $$00000-0001-5462-0676$$aNef, Serge$$b18
000179252 7001_ $$0P:(DE-He78)3fdc3623477264cb5d0e14f256dbfbb8$$aJohann, Pascal$$b19$$udkfz
000179252 7001_ $$aFrühwald, Michael C$$b20
000179252 7001_ $$00000-0001-9740-0788$$aDugas, Martin$$b21
000179252 7001_ $$00000-0002-8731-1121$$aSchüller, Ulrich$$b22
000179252 7001_ $$00000-0002-5676-8102$$aKerl, Kornelius$$b23
000179252 773__ $$0PERI:(DE-600)2553671-0$$a10.1038/s41467-022-29152-4$$gVol. 13, no. 1, p. 1544$$n1$$p1544$$tNature Communications$$v13$$x2041-1723$$y2022
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