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ADAM10 shapes myeloid antigen-presenting cell homeostasis in the splenic marginal zone

ABSTRACT: ADAM10 shapes myeloid antigen-presenting cell homeostasis in the splenic marginal zone

PROVIDER: PRJNA647396 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12271081.fastq.gz	Fastqsanger.gz
	SRR12271082.fastq.gz	Fastqsanger.gz
	SRR12271083.fastq.gz	Fastqsanger.gz
	SRR12271084.fastq.gz	Fastqsanger.gz
	SRR12271085.fastq.gz	Fastqsanger.gz

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ADAM10 shapes myeloid antigen-presenting cell homeostasis in the splenic marginal zone

Project description:The spleen contains phenotypically and functionally distinct cDC1 and cDC2 subpopulations, which each can be divided into several smaller and less-well characterized subsets. Despite advances in understanding the complexity of DC ontogeny and function by transcriptional programming, the significance of post-translational modifications in controlling tissue-specific cDC (subset) immunobiology remains elusive. Here, we identified the cell surface-expressed A-disintegrin-and-metalloproteinase 10 (ADAM10) as an essential regulator of cDC1 and cDC2 homeostasis in the splenic marginal zone (MZ). Mice with a CD11c-specific deletion of ADAM10 (ADAM10ΔCD11c) exhibited a complete loss of splenic ESAMhi cDC2A, because ADAM10 controlled their commitment, differentiation, survival, and EBI2-mediated localization within the MZ. Moreover, we discovered that ADAM10 is a molecular switch regulating cDC2 subset heterogeneity in the spleen, as this unbalanced cDC2A homeostasis in the absence of ADAM10 was compensated for by the emergence of a novel Clec12a+ cDC2B subset, closely resembling cDC2 generally found in peripheral lymph nodes. Moreover, in ADAM10ΔCD11c mice terminal differentiation of cDC1 was abrogated, resulting in reduced numbers of Langerin+ cDC1.

2021-09-06 | GSE154767 | GEO

ADAM10 shapes myeloid antigen-presenting cell homeostasis in the splenic marginal zone

2023-06-27 | GSE154309 | GEO

ADAM10 shapes myeloid antigen-presenting cell homeostasis in the splenic marginal zone

Project description:ADAM10 shapes myeloid antigen-presenting cell homeostasis in the splenic marginal zone

| PRJNA645837 | ENA

Genomic profiling of splenic marginal zone lymphoma (SMZL)

Project description:Array-based comparative genomic hybridization comparing splenic marginal zone lymphoma (SMZL) specimens with control DNA

2014-01-01 | GSE34768 | GEO

Tissue proteomics of splenic marginal zone lymphoma

Project description:Splenic marginal zone lymphoma (SMZL) is a rare chronic B lymphoproliferative disease, whose molecular pathogenesis is still not well established. For the first time a proteomic approach was undertaken to analyse the protein profiles of SMZL tissue. Western blot, immunohistochemical analysis and functional data mining were also performed in order to validate results, classify proteins, and explore their potential relationships. We demonstrated that SMZL is characterized by modulation of proteins related to energetic metabolism and apoptosis pathways. We also reported specific proteins (such as biliverdin reductase A, manganese superoxide dismutase, beta-2 microglobulin, growth factor receptor-bound protein 2, acidic leucine-rich nuclear phosphoprotein 32 family member A, and SET nuclear oncogene) directly involved in NF-kBand BCR pathways, as well as in chromatin remodelling and cytoskeleton. Our findings shed new light on SMZL pathogenesis and provide a basis for the future development of novel biomarkers.

2015-04-23 | PXD001124 | Pride

Human splenic marginal zone precursors (MZP) differentiation into marginal zone B cells (MZB)through a Notch2 signalling pathway

Project description:RNA microarray profiling analysis was performed on different ex-vivo human splenic B cell subsets (M-^SNaM-oveM-^T, marginal zone precursors or M-^SMZPM-^T, marginal zone B cells orM-^T MZBM-^T, M-^SMTG+CD45+M-^T cells) and on M-^Sp27M-^T cells, corresponding to the fraction of MZP cells that differentiated into CD27-expressing cells after culture on OP9-hDLL1 cells cultured with OP9-hDLL1 cells that differentiated into CD27-expressing cells

2014-03-26 | E-MTAB-2244 | biostudies-arrayexpress

Gene expression profiles from human splenic Marginal Zone and Naive (Follicular) B cells

Project description:Splenic Marginal Zone B cells mount innate-like T cell-independent (TI) antibody responses to blood-borne antigens upon receiving activation signals from TACI-engaging factors BAFF and APRIL. The transcriptome analysis of splenic Marginal Zone (MZ) B cells was performed to verify which transcriptional programs are enhanced in the innate-like MZ B cell subset and to study the involvement of mTOR in MZ B cells activated via TACI.

2017-10-14 | GSE85289 | GEO

Posttranslational modifications by ADAM10 shape myeloid antigen-presenting cell homeostasis in the splenic marginal zone.

Project description:The spleen contains phenotypically and functionally distinct conventional dendritic cell (cDC) subpopulations, termed cDC1 and cDC2, which each can be divided into several smaller and less well-characterized subsets. Despite advances in understanding the complexity of cDC ontogeny by transcriptional programming, the significance of posttranslational modifications in controlling tissue-specific cDC subset immunobiology remains elusive. Here, we identified the cell-surface-expressed A-disintegrin-and-metalloproteinase 10 (ADAM10) as an essential regulator of cDC1 and cDC2 homeostasis in the splenic marginal zone (MZ). Mice with a CD11c-specific deletion of ADAM10 (ADAM10ΔCD11c) exhibited a complete loss of splenic ESAMhi cDC2A because ADAM10 regulated the commitment, differentiation, and survival of these cells. The major pathways controlled by ADAM10 in ESAMhi cDC2A are Notch, signaling pathways involved in cell proliferation and survival (e.g., mTOR, PI3K/AKT, and EIF2 signaling), and EBI2-mediated localization within the MZ. In addition, we discovered that ADAM10 is a molecular switch regulating cDC2 subset heterogeneity in the spleen, as the disappearance of ESAMhi cDC2A in ADAM10ΔCD11c mice was compensated for by the emergence of a Clec12a+ cDC2B subset closely resembling cDC2 generally found in peripheral lymph nodes. Moreover, in ADAM10ΔCD11c mice, terminal differentiation of cDC1 was abrogated, resulting in severely reduced splenic Langerin+ cDC1 numbers. Next to the disturbed splenic cDC compartment, ADAM10 deficiency on CD11c+ cells led to an increase in marginal metallophilic macrophage (MMM) numbers. In conclusion, our data identify ADAM10 as a molecular hub on both cDC and MMM regulating their transcriptional programming, turnover, homeostasis, and ability to shape the anatomical niche of the MZ.

| S-EPMC8463803 | biostudies-literature

A single cell RNA-Seq study of splenic marginal zone lymphomas (SMZL)

Project description:Purpose: Single cell RNA-Seq was used to characterize in depth splenic samples obtained from splenic marginal zone lymphomas Methods: 3 frozen samples of spleen from SMZL patients were selected and thawed for performing a 10X genomics single cell RNA-Sequencing 3' assay. Results: Tumor cells formed mainly patient specific-B cell clusters, while T-cells from the 3 patients clustered together. Conclusion: Single RNA-Seq unveils the cellular composition of splenic tumors from SMZL patients.

2021-10-31 | GSE175785 | GEO

RNA-seq analysis of splenic follicular IgD low and IgD high, and marginal zone B cells

Project description:RNA sequencing was performed to determine the uniqueness of splenic follicular IgD low B cells compared to splenic follicular IgD high and marginal zone B cells.

2018-12-03 | GSE111911 | GEO

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