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The tumor microenvironment shows a hierarchy of cell-cell interactions dominated by fibroblasts

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE218197 | GEO | 2023/08/27

REPOSITORIES: GEO

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The tumor microenvironment shows a hierarchy of cell-cell interactions dominated by fibroblasts.

Project description:The tumor microenvironment (TME) is comprised of non-malignant cells that interact with each other and with cancer cells, critically impacting cancer biology. The TME is complex, and understanding it requires simplifying approaches. Here we provide an experimental-mathematical approach to decompose the TME into small circuits of interacting cell types. We find, using female breast cancer single-cell-RNA-sequencing data, a hierarchical network of interactions, with cancer-associated fibroblasts (CAFs) at the top secreting factors primarily to tumor-associated macrophages (TAMs). This network is composed of repeating circuit motifs. We isolate the strongest two-cell circuit motif by culturing fibroblasts and macrophages in-vitro, and analyze their dynamics and transcriptomes. This isolated circuit recapitulates the hierarchy of in-vivo interactions, and enables testing the effect of ligand-receptor interactions on cell dynamics and function, as we demonstrate by identifying a mediator of CAF-TAM interactions - RARRES2, and its receptor CMKLR1. Thus, the complexity of the TME may be simplified by identifying small circuits, facilitating the development of strategies to modulate the TME.

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The tumor microenvironment shows a hierarchy of cell-cell interactions dominated by fibroblasts [cancer CM]

Project description:We preformed RNA seq on invitro fibroblasts after mono-cultured or co-cultured with macrophages in DMEM or with 4T1-conditioned medium , In order to understand the affect of cancer on macrophages-fibroblasts interactions

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The tumor microenvironment shows a hierarchy of cell-cell interactions dominated by fibroblasts

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