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A draft network of ligand–receptor-mediated multicellular signalling in human

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  • Jordan A. Ramilowski

    (RIKEN Center for Life Science Technologies)

  • Tatyana Goldberg

    (Technische Universität München (TUM)
    TUM Graduate School, Center of Doctoral Studies in Informatics and its Applications (CeDoSIA))

  • Jayson Harshbarger

    (RIKEN Center for Life Science Technologies)

  • Edda Kloppmann

    (Technische Universität München (TUM))

  • Marina Lizio

    (RIKEN Center for Life Science Technologies)

  • Venkata P. Satagopam

    (Luxembourg Centre for Systems Biomedicine, Campus Belval)

  • Masayoshi Itoh

    (RIKEN Center for Life Science Technologies
    RIKEN Preventive Medicine and Diagnosis Innovation Program)

  • Hideya Kawaji

    (RIKEN Center for Life Science Technologies
    RIKEN Preventive Medicine and Diagnosis Innovation Program)

  • Piero Carninci

    (RIKEN Center for Life Science Technologies)

  • Burkhard Rost

    (Technische Universität München (TUM)
    TUM Graduate School, Center of Doctoral Studies in Informatics and its Applications (CeDoSIA))

  • Alistair R. R. Forrest

    (RIKEN Center for Life Science Technologies
    Harry Perkins Institute of Medical Research, QEII Medical Centre and Centre for Medical Research, the University of Western Australia, PO Box 7214, 6 Verdun Street, Nedlands, Perth, Western Australia 6008, Australia)

Abstract

Cell-to-cell communication across multiple cell types and tissues strictly governs proper functioning of metazoans and extensively relies on interactions between secreted ligands and cell-surface receptors. Herein, we present the first large-scale map of cell-to-cell communication between 144 human primary cell types. We reveal that most cells express tens to hundreds of ligands and receptors to create a highly connected signalling network through multiple ligand–receptor paths. We also observe extensive autocrine signalling with approximately two-thirds of partners possibly interacting on the same cell type. We find that plasma membrane and secreted proteins have the highest cell-type specificity, they are evolutionarily younger than intracellular proteins, and that most receptors had evolved before their ligands. We provide an online tool to interactively query and visualize our networks and demonstrate how this tool can reveal novel cell-to-cell interactions with the prediction that mast cells signal to monoblastic lineages via the CSF1–CSF1R interacting pair.

Suggested Citation

  • Jordan A. Ramilowski & Tatyana Goldberg & Jayson Harshbarger & Edda Kloppmann & Marina Lizio & Venkata P. Satagopam & Masayoshi Itoh & Hideya Kawaji & Piero Carninci & Burkhard Rost & Alistair R. R. F, 2015. "A draft network of ligand–receptor-mediated multicellular signalling in human," Nature Communications, Nature, vol. 6(1), pages 1-12, November.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms8866
    DOI: 10.1038/ncomms8866
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