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cell, cells, ligands, receptors, article, pairs, proteins, google, scholar, data, signalling, expression, cas, types, receptor, ligandreceptor, supplementary, protein, primary, expressed, ligand, genes, gene, analysis, fig, human, set, tpm, nature, celltocell, communication, lineages, haematopoietic, age, secreted, levels, network, found, interactions, subcellular, number, enrichment, localization, interacting, pair, average, proteome, enriched, type, fantom,

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nature portfolio org/pub/databases/uniprot/current_release/knowledgebase/proteomes/ privacy policy open source tools ch/download/protected/string_9_1/protein advertising io/connectome ligand–receptor-mediated multicellular signalling open source software social media author edda kloppmann mann–whitney u-test-adjusted healthy middle-aged fantom5 cage libraries p-pod’s22 orthomcl23 clustering 0/ reprints ligand-dependent development pre-computed estimates based nature 444 nature 507 nature 509 nature middle panel shows mann–whitney u-test drd4/bdnf gene-gene interaction correctly post-translationally modified cancer research trust cell-type-specific expression profiles rna-seq data sets lineage-specific growth factor cell-type-restricted expression profiles protein phosphorylation/modification terms capture spatial relationships58 influences t-cell accumulation ccr9 beta-chemokine receptor org/cgi-bin/hgnc_downloads cell-type-restricted expression showed jp/5/suppl/ramilowski_et_al_2015/data/ csf1–csf1r ligand–receptor pair fantom5 b-cell transcriptome early embryonic development public protein–protein interaction computational tools loctree3 jp/5/suppl/ramilowski_et_al_2015/vis jp/5/suppl/ramilowski_et_al_2015/vis/ protein–protein interaction networks cell-type-specific pm proteins libraries human protein-coding genes receptor–ligand pairs form

Questions {❓}

• The evolution of multicellularity: a minor major transition?

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         description: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. Cell-to-cell communication relies upon interactions between secreted ligands and cell surface receptors. Here, Ramilowski et al.present a draft cell-to-cell communication network based on expression of ligand-receptor pairs in 144 different human cell types.
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               name:Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan
               type:PostalAddress
            type:Organization
      name:Burkhard Rost
      affiliation:
            name:Technische Universität München (TUM)
            address:
               name:Department for Bioinformatics and Computational Biology-I12, Technische Universität München (TUM), Garching, Germany
               type:PostalAddress
            type:Organization
            name:TUM Graduate School, Center of Doctoral Studies in Informatics and its Applications (CeDoSIA)
            address:
               name:TUM Graduate School, Center of Doctoral Studies in Informatics and its Applications (CeDoSIA), Garching, Germany
               type:PostalAddress
            type:Organization
      name:Alistair R. R. Forrest
      affiliation:
            name:RIKEN Center for Life Science Technologies
            address:
               name:Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan
               type:PostalAddress
            type:Organization
            name: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
            address:
               name: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,
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan
      name:Department for Bioinformatics and Computational Biology-I12, Technische Universität München (TUM), Garching, Germany
      name:TUM Graduate School, Center of Doctoral Studies in Informatics and its Applications (CeDoSIA), Garching, Germany
      name:Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan
      name:Department for Bioinformatics and Computational Biology-I12, Technische Universität München (TUM), Garching, Germany
      name:Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan
      name:Luxembourg Centre for Systems Biomedicine, Campus Belval, Luxembourg
      name:Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan
      name:RIKEN Preventive Medicine and Diagnosis Innovation Program, Saitama, Japan
      name:Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan
      name:RIKEN Preventive Medicine and Diagnosis Innovation Program, Saitama, Japan
      name:Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan
      name:Department for Bioinformatics and Computational Biology-I12, Technische Universität München (TUM), Garching, Germany
      name:TUM Graduate School, Center of Doctoral Studies in Informatics and its Applications (CeDoSIA), Garching, Germany
      name:Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan
      name: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,

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