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Temporal and spatial topography of cell proliferation in cancer.

Nature cell biology | 2022

Proliferation is a fundamental trait of cancer cells, but its properties and spatial organization in tumours are poorly characterized. Here we use highly multiplexed tissue imaging to perform single-cell quantification of cell cycle regulators and then develop robust, multivariate, proliferation metrics. Across diverse cancers, proliferative architecture is organized at two spatial scales: large domains, and smaller niches enriched for specific immune lineages. Some tumour cells express cell cycle regulators in the (canonical) patterns expected of freely growing cells, a phenomenon we refer to as 'cell cycle coherence'. By contrast, the cell cycles of other tumour cell populations are skewed towards specific phases or exhibit non-canonical (incoherent) marker combinations. Coherence varies across space, with changes in oncogene activity and therapeutic intervention, and is associated with aggressive tumour behaviour. Thus, multivariate measures from high-plex tissue images capture clinically significant features of cancer proliferation, a fundamental step in enabling more precise use of anti-cancer therapies.

Pubmed ID: 35292783 RIS Download

Research resources used in this publication

None found

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Associated grants

  • Agency: NCI NIH HHS, United States
    Id: U54 CA225088
  • Agency: NCI NIH HHS, United States
    Id: R41 CA224503
  • Agency: NHLBI NIH HHS, United States
    Id: T32 HL007627
  • Agency: NCI NIH HHS, United States
    Id: P50 CA168504
  • Agency: NCI NIH HHS, United States
    Id: R35 CA210057
  • Agency: NCI NIH HHS, United States
    Id: K08 CA191058
  • Agency: NCI NIH HHS, United States
    Id: R01 CA194005
  • Agency: NCI NIH HHS, United States
    Id: P50 CA165962
  • Agency: NCI NIH HHS, United States
    Id: P30 CA006516
  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007748

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RRID:SCR_006307

A cloud-based collaborative platform which co-locates data, code, and computing resources for analyzing genome-scale data and seamlessly integrates these services allowing scientists to share and analyze data together. Synapse consists of a web portal integrated with the R/Bioconductor statistical package and will be integrated with additional tools. The web portal is organized around the concept of a Project which is an environment where you can interact, share data, and analysis methods with a specific group of users or broadly across open collaborations. Projects provide an organizational structure to interact with data, code and analyses, and to track data provenance. A project can be created by anyone with a Synapse account and can be shared among all Synapse users or restricted to a specific team. Public data projects include the Synapse Commons Repository (SCR) (syn150935) and the metaGenomics project (syn275039). The SCR provides access to raw data and phenotypic information for publicly available genomic data sets, such as GEO and TCGA. The metaGenomics project provides standardized preprocessed data and precomputed analysis of the public SCR data.

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