RRC ID 72302
Author Gaultier C, Foppolo S, Maurange C.
Title Regulation of developmental hierarchy in Drosophila neural stem cell tumors by COMPASS and Polycomb complexes.
Journal Sci Adv
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.
Volume 8(19)
Pages eabi4529
Published 2022-5-13
DOI 10.1126/sciadv.abi4529
PMID 35544555
PMC PMC9094666
MeSH Animals Drosophila / genetics Drosophila Proteins* / metabolism Drosophila melanogaster / genetics Gene Expression Regulation, Developmental Larva / genetics Neoplasms* / genetics Neural Stem Cells* / metabolism Polycomb-Group Proteins / genetics
IF 13.117