Supplementary data for: Ligand-specific tuning of CLEC10A signalling strength and dendritic cell responses through engagement of different GalNAc-containing glycan structures
Data files
Nov 04, 2025 version files 11.03 MB
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README.md
4.79 KB
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Supporting_information_v3.pdf
1.04 MB
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Table_S1_DESeq2_Differential_Expression_Tables.xlsx
9.66 MB
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Table_S2_GO_term_analysis.xlsx
329.77 KB
Abstract
C-type lectin receptors on dendritic cells shape immune responses to pathogens and tumour cells through the specific recognition of glycans. C-type lectin domain family 10 member A [CLEC10A; also known as macrophage galactose-type lectin (MGL)] binds terminal N-Acetylgalactosamine (GalNAc) residues, which are often highly exposed on tumours. Signalling through this receptor increases interleukin-10 (IL-10) and tumour necrosis factor alpha production by monocyte-derived dendritic cells (moDCs), which promotes a T helper 2 (Th2) or type 1 regulatory T cell (Tr1) response. Recently, several CLEC10A glycan ligands were identified that induce distinct conformational changes in the CLEC10A carbohydrate-recognition domain, but their ability to alter moDC function has not been thoroughly explored. Here, we used CLEC10A ligand glycodendrimers to investigate the transcriptional responses induced by the CLEC10A ligands previously modelled, and determined how these transcriptional programs were associated with the cellular moDC responses. The CLEC10A ligand dendrimers varied in their affinity for CLEC10A and their capacity to increase IL-10 produced by moDCs. Although all glycodendrimers induced differential gene expression, this was strongest for the Forssman antigen dendrimer. The volcano plots and gene lists from this analysis are included in the supporting data provided here. The gene ontology (GO) terms associated with genes detected across ligands related to mitogen-activated protein kinase (MAPK) signalling, chemotaxis, apoptosis, angiogenesis, cytokine production and CD4+ T cell differentiation, as seen in the supporting table 2. The CLEC10A ligand dendrimers also altered the chemokine profile secreted by moDCs. Furthermore, these glycodendrimers increased the percentage of C-C chemokine receptor type 7 (CCR7)-expressing moDCs, which was prevented by inhibiting CLEC10A signalling. Overall, there was limited evidence for glycan-specific signalling via CLEC10A, but the glycans did alter the magnitude of the CLEC10A-mediated responses.
Dataset DOI: 10.5061/dryad.gmsbcc30j
Description of the data and file structure
Supplementary data associated with the paper "**Ligand-specific tuning of CLEC10A signalling strength and dendritic cell responses through engagement of different GalNAc-containing glycan structures". **
Files and variables
File: Supporting_information_v3.pdf
Description: Combined PDF containing 1 supporting figure and supporting tables 3 & 4. The descriptions of supporting tables 1&2 are included as well.
In supporting table 4, the aGM2 dendrimer was not included for the detection of chemokines (second part of the table) because this dendrimer had no biological effect in any of the previous analyses. These cells were therefore left empty in the table.
File: Table_S1_DESeq2_Differential_Expression_Tables.xlsx
Description: Significant differentially expressed genes on mRNA level for moDCs stimulated with CLEC10A ligand glycodendrimers compared to a control dendrimer. Each CLEC10A dendrimer is compared to the control dendrimer in a separate tab labeled Control_"Dendrimer in analysis".
Variables
- ENSEMBL: ENSEMBL number of each gene in the analysis.
- BaseMean: displays the mean normalized gene expression for the control dendrimer.
- Log2FoldChange: displays the log-transformed change in expression of the control dendrimer minus the specific glycodendrimer.
- lfcSE: the standard error of the Log2FoldChange.
- stat: the test statistic. The Log2FoldChange and lfcSE are used to create this test statistic.
- pvalue: the p-value corresponding to the test statistic.
- padj: column contained the pvalues adjusted for multiple comparisons. Genes with padj < 0.05 were considered as significantly differentially expressed. The padj column has the value #N/B if no padj could be calculated.
- GeneName: the HGNC symbols of the genes in the analysis. These are the commonly used biological names of the genes. The GeneName column was given the value n/a if no HGNC symbol is associated with the ENSEMBL number.
File: Table_S2_GO_term_analysis.xlsx
Description: Gene ontology terms that are associated with the significant differentially expressed genes for each glycodendrimer. The upregulated and downregulated genes for the Forssman antigen, GalNAc, blood group A antigen and GM2 dendrimer are in seperate tabs, named for the specific dendrimer and up/down. The CLEC10A core genes, overlapping genes between the GalNAc and Forssman antigen (Forss & GalNAc) and Forssman specific (Forss specific) DEGs were also included.
The overview page displays the GO terms displayed in figure 3C of the paper and the associated -log10 p-values. The p-values were not significant (-Log(10) Pvalue < 5) for the cells labelled n/s.
Variables
For the overview tab:
- ID: GO number from the GO database.
- Term: name associated with the GO number
- -Log(10) Pvalue Forssman: the -log10 p-value for the GO term for the Forssman dendrimer specifically. n/s means not significant.
- -Log(10) Pvalue GalNAc: the -log10 p-value for the GO term for the GalNAc dendrimer specifically. n/s means not significant.
- -Log(10) Pvalue BGA: the -log10 p-value for the GO term for the blood group A antigen dendrimer specifically. n/s means not significant.
- -Log(10) Pvalue GM2: the -log10 p-value for the GO term for the GM2 dendrimer specifically. n/s means not significant.
For the remaining tabs:
- ID: GO number from the GO database.
- GOGroups: the umbrella group in which the GO term was placed during the analysis.
- Term: name associated with the GO number
- Term PValue: p-value for each GO term. P<0.05 was used as cut-off for significant GO terms.
- Term PValue Corrected with Benjamini-Hochberg: the p-values with Benjamini-Hochberg correction. P<0.05 was used as cut-off for significant GO terms.
- -Log(10) PValue: the -log10- transformed values of the corrected p-values from column E, the p-values with Benjamini-Hochberg correction.
- % Associated Genes: Each term has a list of genes associated with it prepared beforehand. The % Associated Genes displays the percentage of genes from this list that were found in the current analysis of differentially expressed genes.
- Nr. Genes: the number of genes from the associated gene list that were found in the current analysis of differentially expressed genes.
- Associated Genes Found: the HGNC symbols of the genes, associated with the GO term, that were found in the differentially expressed genes from the current analysis.