Limits...
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

Summary statistics of ligand and receptor usage in human primary cells.(a,b) Each data-point corresponds to a primary cell type. Colours indicate broad lineage classes. (a) Number of ligands (x-axis) versus numbers of receptors (y-axis) expressed in each cell type. (b) Autocrine signalling in primary cell types. X-axis shows the fraction of ligands expressed by a given cell where the receptor is also expressed on the same cell. Y-axis shows the reciprocal for the fraction of receptors on a given cell where the ligand is also expressed. The red lines in a,b show the mean numbers of ligands or receptors in each plot. (c) Density plot showing the number of cells in which each cognate ligand–receptor pair is expressed. Medians are shown as green lines. For all plots in a–c a threshold of 10 TPM was used. (d) Distribution of the number of possible ligand–receptor paths between ligand-secreting cell A and receptor-expressing cell B calculated for all 144 × 144 possible cell-pair permutations across 10, 50 and 100 TPM CAGE detection thresholds.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4525178&req=5

f3: Summary statistics of ligand and receptor usage in human primary cells.(a,b) Each data-point corresponds to a primary cell type. Colours indicate broad lineage classes. (a) Number of ligands (x-axis) versus numbers of receptors (y-axis) expressed in each cell type. (b) Autocrine signalling in primary cell types. X-axis shows the fraction of ligands expressed by a given cell where the receptor is also expressed on the same cell. Y-axis shows the reciprocal for the fraction of receptors on a given cell where the ligand is also expressed. The red lines in a,b show the mean numbers of ligands or receptors in each plot. (c) Density plot showing the number of cells in which each cognate ligand–receptor pair is expressed. Medians are shown as green lines. For all plots in a–c a threshold of 10 TPM was used. (d) Distribution of the number of possible ligand–receptor paths between ligand-secreting cell A and receptor-expressing cell B calculated for all 144 × 144 possible cell-pair permutations across 10, 50 and 100 TPM CAGE detection thresholds.

Mentions: Broadly classifying the cell types using cell ontologies37 into endothelial, epithelial, haematopoietic, mesenchymal, nervous system and other lineages, and reviewing their ligand/receptor expression profiles, we observed that the blood lineages appeared to be outliers in that they express less ligands on average (∼92, ∼51, ∼36 ligands at 10, 50, 100 TPM, respectively; Mann–Whitney U-test P values<0.001) and less receptors on average (∼120 receptors at 10 TPM; Mann–Whitney U-test P value<0.001) compared with the other lineages (Fig. 3a, Supplementary Fig. 6a,b). This suggests that immune cells use fewer paths to broadcast their state to their neighbours. We also observe that on average two-thirds of ligands and receptors expressed from any given cell can potentially bind to at least one of its cognate partners on the same cell type (Fig. 3b), indicating that the extent of autocrine signalling is significant.


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)

Summary statistics of ligand and receptor usage in human primary cells.(a,b) Each data-point corresponds to a primary cell type. Colours indicate broad lineage classes. (a) Number of ligands (x-axis) versus numbers of receptors (y-axis) expressed in each cell type. (b) Autocrine signalling in primary cell types. X-axis shows the fraction of ligands expressed by a given cell where the receptor is also expressed on the same cell. Y-axis shows the reciprocal for the fraction of receptors on a given cell where the ligand is also expressed. The red lines in a,b show the mean numbers of ligands or receptors in each plot. (c) Density plot showing the number of cells in which each cognate ligand–receptor pair is expressed. Medians are shown as green lines. For all plots in a–c a threshold of 10 TPM was used. (d) Distribution of the number of possible ligand–receptor paths between ligand-secreting cell A and receptor-expressing cell B calculated for all 144 × 144 possible cell-pair permutations across 10, 50 and 100 TPM CAGE detection thresholds.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Summary statistics of ligand and receptor usage in human primary cells.(a,b) Each data-point corresponds to a primary cell type. Colours indicate broad lineage classes. (a) Number of ligands (x-axis) versus numbers of receptors (y-axis) expressed in each cell type. (b) Autocrine signalling in primary cell types. X-axis shows the fraction of ligands expressed by a given cell where the receptor is also expressed on the same cell. Y-axis shows the reciprocal for the fraction of receptors on a given cell where the ligand is also expressed. The red lines in a,b show the mean numbers of ligands or receptors in each plot. (c) Density plot showing the number of cells in which each cognate ligand–receptor pair is expressed. Medians are shown as green lines. For all plots in a–c a threshold of 10 TPM was used. (d) Distribution of the number of possible ligand–receptor paths between ligand-secreting cell A and receptor-expressing cell B calculated for all 144 × 144 possible cell-pair permutations across 10, 50 and 100 TPM CAGE detection thresholds.
Mentions: Broadly classifying the cell types using cell ontologies37 into endothelial, epithelial, haematopoietic, mesenchymal, nervous system and other lineages, and reviewing their ligand/receptor expression profiles, we observed that the blood lineages appeared to be outliers in that they express less ligands on average (∼92, ∼51, ∼36 ligands at 10, 50, 100 TPM, respectively; Mann–Whitney U-test P values<0.001) and less receptors on average (∼120 receptors at 10 TPM; Mann–Whitney U-test P value<0.001) compared with the other lineages (Fig. 3a, Supplementary Fig. 6a,b). This suggests that immune cells use fewer paths to broadcast their state to their neighbours. We also observe that on average two-thirds of ligands and receptors expressed from any given cell can potentially bind to at least one of its cognate partners on the same cell type (Fig. 3b), indicating that the extent of autocrine signalling is significant.

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