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- W4280490329 abstract "COMPASS and Polycomb complexes are antagonistic chromatin complexes that are frequently inactivated in cancers, but how these events affect the cellular hierarchy, composition, and growth of tumors is unclear. These characteristics can be systematically investigated in Drosophila neuroblast tumors in which cooption of temporal patterning induces a developmental hierarchy that confers cancer stem cell (CSC) properties to a subset of neuroblasts retaining an early larval temporal identity. Here, using single-cell transcriptomics, we reveal that the trithorax/MLL1/2-COMPASS-like complex guides the developmental trajectory at the top of the tumor hierarchy. Consequently, trithorax knockdown drives larval-to-embryonic temporal reversion and the marked expansion of CSCs that remain locked in a spectrum of early temporal states. Unexpectedly, this phenotype is amplified by concomitant inactivation of Polycomb repressive complex 2 genes, unleashing tumor growth. This study illustrates how inactivation of specific COMPASS and Polycomb complexes cooperates to impair tumor hierarchies, inducing CSC plasticity, heterogeneity, and expansion." @default.
- W4280490329 created "2022-05-22" @default.
- W4280490329 creator A5017585908 @default.
- W4280490329 creator A5020818980 @default.
- W4280490329 creator A5029566539 @default.
- W4280490329 date "2022-05-13" @default.
- W4280490329 modified "2023-10-17" @default.
- W4280490329 title "Regulation of developmental hierarchy in <i>Drosophila</i> neural stem cell tumors by COMPASS and Polycomb complexes" @default.
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- W4280490329 doi "https://doi.org/10.1126/sciadv.abi4529" @default.
- W4280490329 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35544555" @default.
- W4280490329 hasPublicationYear "2022" @default.
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