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

Ramilowski JA, Goldberg T, Harshbarger J, Kloppman E, Lizio M, Satagopam VP, Itoh M, Kawaji H, Carninci P, Rost B, Forrest AR - Nat Commun (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045 Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Ligand–receptor signalling network interface (hive view).The results of a search for the CSF1–CSF1R ligand–receptor pair, filtered for the top cell-to-cell paths (ranked by the product of CSF1 and CSF1R expression). In this network, stimulated mast cells express the highest levels of CSF1 (1,109 TPM), while CD14+ derived endothelial progenitor cells express the highest levels of CSF1R (699 TPM). Users can select cells and/or ligand–receptor (LR) pairs of interest and filter edges and nodes based on expression levels of L and R. The interface is available at: http://fantom.gsc.riken.jp/5/suppl/Ramilowski_et_al_2015/.
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f4: Ligand–receptor signalling network interface (hive view).The results of a search for the CSF1–CSF1R ligand–receptor pair, filtered for the top cell-to-cell paths (ranked by the product of CSF1 and CSF1R expression). In this network, stimulated mast cells express the highest levels of CSF1 (1,109 TPM), while CD14+ derived endothelial progenitor cells express the highest levels of CSF1R (699 TPM). Users can select cells and/or ligand–receptor (LR) pairs of interest and filter edges and nodes based on expression levels of L and R. The interface is available at: http://fantom.gsc.riken.jp/5/suppl/Ramilowski_et_al_2015/.

Mentions: Using the ligand and receptor pairs described above, we then calculated all cell-to-cell edges where both ligand and receptor were expressed in at least one primary cell state (≥10 TPM). To benefit the research community, we provide an online resource that visualizes on demand cell-to-cell networks for any given ligand–receptor pair across all 144 primary cell types. The tool allows users to select primary cells and ligand–receptor pairs to be visualized, and then filters the edges (receptor expression × ligand expression) and nodes (cells) based on the expression levels. Visualized networks can be downloaded as SVG (scalable vector graphics) or in a data format compatible with other network visualization platforms such as Cytoscape39 and Gephi40 for additional exploration. In Fig. 4, we show an example of top cells communicating via the CSF1 ligand–CSF1R receptor pair, where mast cells are the major broadcasters (the highest levels of CSF1 expression), and monocytes and related cells are the major recipients (the highest levels of CSF1R expression) of these signals. We also note that monocyte-derived macrophages demonstrate autocrine signalling via this pair, expressing both CSF1 and CSF1R at notable levels. Additional use cases are provided in Supplementary Note 1.


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

Ramilowski JA, Goldberg T, Harshbarger J, Kloppman E, Lizio M, Satagopam VP, Itoh M, Kawaji H, Carninci P, Rost B, Forrest AR - Nat Commun (2015)

Ligand–receptor signalling network interface (hive view).The results of a search for the CSF1–CSF1R ligand–receptor pair, filtered for the top cell-to-cell paths (ranked by the product of CSF1 and CSF1R expression). In this network, stimulated mast cells express the highest levels of CSF1 (1,109 TPM), while CD14+ derived endothelial progenitor cells express the highest levels of CSF1R (699 TPM). Users can select cells and/or ligand–receptor (LR) pairs of interest and filter edges and nodes based on expression levels of L and R. The interface is available at: http://fantom.gsc.riken.jp/5/suppl/Ramilowski_et_al_2015/.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4525178&req=5

f4: Ligand–receptor signalling network interface (hive view).The results of a search for the CSF1–CSF1R ligand–receptor pair, filtered for the top cell-to-cell paths (ranked by the product of CSF1 and CSF1R expression). In this network, stimulated mast cells express the highest levels of CSF1 (1,109 TPM), while CD14+ derived endothelial progenitor cells express the highest levels of CSF1R (699 TPM). Users can select cells and/or ligand–receptor (LR) pairs of interest and filter edges and nodes based on expression levels of L and R. The interface is available at: http://fantom.gsc.riken.jp/5/suppl/Ramilowski_et_al_2015/.
Mentions: Using the ligand and receptor pairs described above, we then calculated all cell-to-cell edges where both ligand and receptor were expressed in at least one primary cell state (≥10 TPM). To benefit the research community, we provide an online resource that visualizes on demand cell-to-cell networks for any given ligand–receptor pair across all 144 primary cell types. The tool allows users to select primary cells and ligand–receptor pairs to be visualized, and then filters the edges (receptor expression × ligand expression) and nodes (cells) based on the expression levels. Visualized networks can be downloaded as SVG (scalable vector graphics) or in a data format compatible with other network visualization platforms such as Cytoscape39 and Gephi40 for additional exploration. In Fig. 4, we show an example of top cells communicating via the CSF1 ligand–CSF1R receptor pair, where mast cells are the major broadcasters (the highest levels of CSF1 expression), and monocytes and related cells are the major recipients (the highest levels of CSF1R expression) of these signals. We also note that monocyte-derived macrophages demonstrate autocrine signalling via this pair, expressing both CSF1 and CSF1R at notable levels. Additional use cases are provided in Supplementary Note 1.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045 Japan.

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.

No MeSH data available.


Related in: MedlinePlus