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Trends Biotechnol. 2016 Aug;34(8):627-637. doi: 10.1016/j.tibtech.2016.02.016. Epub 2016 Apr 14.

Systems Biology Analysis of Heterocellular Signaling.

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The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address:


Tissues comprise multiple heterotypic cell types (e.g., epithelial, mesenchymal, and immune cells). Communication between heterotypic cell types is essential for biological cohesion and is frequently dysregulated in disease. Despite the importance of heterocellular communication, most systems biology techniques do not report cell-specific signaling data from mixtures of cells. As a result, our existing perspective of cellular behavior under-represents the influence of heterocellular signaling. Recent technical advances now permit the resolution of systems-level cell-specific signaling data. This review discusses how new physical, spatial, and isotopic resolving methods are facilitating unique systems biology studies of heterocellular communication.


PTM; cell signaling; cell–cell communication; heterocellular; mass cytometry; phosphoproteomics; systems biology

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