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Nat Commun. 2015 Jul 22;6:7866. doi: 10.1038/ncomms8866.

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

Author information

1
RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045 Japan.
2
1] Department for Bioinformatics and Computational Biology-I12, Technische Universität München (TUM), Boltzmannstrasse 3, 85748 Garching, Germany [2] TUM Graduate School, Center of Doctoral Studies in Informatics and its Applications (CeDoSIA), Boltzmannstrasse 11, 85748 Garching, Germany.
3
Department for Bioinformatics and Computational Biology-I12, Technische Universität München (TUM), Boltzmannstrasse 3, 85748 Garching, Germany.
4
Luxembourg Centre for Systems Biomedicine, Campus Belval, 7 Avenue des Hauts Fourneaux, L-4362 Belval, Luxembourg.
5
1] RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045 Japan [2] RIKEN Preventive Medicine and Diagnosis Innovation Program, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
6
1] RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045 Japan [2] 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.

PMID:
26198319
PMCID:
PMC4525178
DOI:
10.1038/ncomms8866
[Indexed for MEDLINE]
Free PMC Article

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