Dataset Information

Regulation of developmental hierarchy in Drosophila neural stem cell tumors by COMPASS and Polycomb complexes.

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.

SUBMITTER: Gaultier C

PROVIDER: S-EPMC9094666 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Regulation of developmental hierarchy in <i>Drosophila</i> neural stem cell tumors by COMPASS and Polycomb complexes.

Gaultier Cassandra C Foppolo Sophie S Maurange Cédric C

Science advances 20220511 19

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 <i>Drosophila</i> 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. ...[more]

PMID: 35544555

Similar Datasets

Project description:IntroductionInvestigating the pathological mechanisms of developmental disorders is a challenge because the symptoms are a result of complex and dynamic factors such as neural networks, cognitive behavior, environment, and developmental learning. Recently, computational methods have started to provide a unified framework for understanding developmental disorders, enabling us to describe the interactions among those multiple factors underlying symptoms. However, this approach is still limited because most studies to date have focused on cross-sectional task performance and lacked the perspectives of developmental learning. Here, we proposed a new research method for understanding the mechanisms of the acquisition and its failures in hierarchical Bayesian representations using a state-of-the-art computational model, referred to as in silico neurodevelopment framework for atypical representation learning.MethodsSimple simulation experiments were conducted using the proposed framework to examine whether manipulating the neural stochasticity and noise levels in external environments during the learning process can lead to the altered acquisition of hierarchical Bayesian representation and reduced flexibility.ResultsNetworks with normal neural stochasticity acquired hierarchical representations that reflected the underlying probabilistic structures in the environment, including higher-order representation, and exhibited good behavioral and cognitive flexibility. When the neural stochasticity was high during learning, top-down generation using higher-order representation became atypical, although the flexibility did not differ from that of the normal stochasticity settings. However, when the neural stochasticity was low in the learning process, the networks demonstrated reduced flexibility and altered hierarchical representation. Notably, this altered acquisition of higher-order representation and flexibility was ameliorated by increasing the level of noises in external stimuli.DiscussionThese results demonstrated that the proposed method assists in modeling developmental disorders by bridging between multiple factors, such as the inherent characteristics of neural dynamics, acquisitions of hierarchical representation, flexible behavior, and external environment.

Dataset Information

Regulation of developmental hierarchy in Drosophila neural stem cell tumors by COMPASS and Polycomb complexes.

Publications

Regulation of developmental hierarchy in <i>Drosophila</i> neural stem cell tumors by COMPASS and Polycomb complexes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets