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Notch signaling facilitates in vitro generation of cross-presenting classical dendritic cells

ABSTRACT: Notch signaling facilitates in vitro generation of cross-presenting classical dendritic cells

PROVIDER: PRJNA434005 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6724180.fastq.gz	Fastqsanger.gz
	SRR6724181.fastq.gz	Fastqsanger.gz
	SRR6724182.fastq.gz	Fastqsanger.gz
	SRR6724175.fastq.gz	Fastqsanger.gz
	SRR6724176.fastq.gz	Fastqsanger.gz

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Notch signaling facilitates in vitro generation of cross-presenting classical dendritic cells

Project description:The IRF8-dependent subset of classical dendritic cells (cDC), termed cDC1, is important for cross-priming cytotoxic T cell responses against pathogens and tumors. Culture of hematopoietic progenitors with DC growth factor Flt3 ligand (Flt3L) yields very few cDC1 (in humans) or only immature "cDC1-like" cells (in the mouse). We report that OP9 stromal cells expressing Notch ligand Delta-like 1 (OP9-DL1) optimize Flt3L-driven development of cDC1 from murine immortalized progenitors and primary bone marrow cells. Co-culture with OP9-DL1 induced IRF8-dependent cDC1 with the phenotype (CD103+ Dec205+ CD8α+) and expression profile resembling ex vivo cDC1. OP9-DL1-induced cDC1 showed preferential migration towards Ccr7 ligands in vitro and superior T cell cross-priming and antitumor vaccination in vivo. Co-culture with OP9-DL1 also greatly increased the yield of IRF8-dependent CD141+ cDC1 from human bone marrow progenitors cultured with Flt3L. Thus, Notch signaling optimizes cDC generation in vitro and yields authentic cDC1 for functional studies and therapeutic applications.

2018-06-05 | GSE110577 | GEO

Transcription factor Etv6 controls functional differentiation of cross-presenting classical dendritic cells

Project description:Transcription factor Etv6 controls functional differentiation of cross-presenting classical dendritic cells

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Notch Signaling Facilitates In Vitro Generation of Cross-Presenting Classical Dendritic Cells.

Project description:The IRF8-dependent subset of classical dendritic cells (cDCs), termed cDC1, is important for cross-priming cytotoxic T cell responses against pathogens and tumors. Culture of hematopoietic progenitors with DC growth factor FLT3 ligand (FLT3L) yields very few cDC1s (in humans) or only immature "cDC1-like" cells (in the mouse). We report that OP9 stromal cells expressing the Notch ligand Delta-like 1 (OP9-DL1) optimize FLT3L-driven development of cDC1s from murine immortalized progenitors and primary bone marrow cells. Co-culture with OP9-DL1 induced IRF8-dependent cDC1s with a phenotype (CD103+ Dec205+ CD8α+) and expression profile resembling primary splenic cDC1s. OP9-DL1-induced cDC1s showed preferential migration toward CCR7 ligands in vitro and superior T cell cross-priming and antitumor vaccination in vivo. Co-culture with OP9-DL1 also greatly increased the yield of IRF8-dependent CD141+ cDC1s from human bone marrow progenitors cultured with FLT3L. Thus, Notch signaling optimizes cDC generation in vitro and yields authentic cDC1s for functional studies and translational applications.

| S-EPMC6063084 | biostudies-literature

Transcription factor Etv6 controls functional differentiation of cross-presenting classical dendritic cells [RNA-Seq]

Project description:Transcription factor Etv6 controls functional differentiation of cross-presenting classical dendritic cells [RNA-Seq]

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Transcription factor Etv6 controls functional differentiation of cross-presenting classical dendritic cells [ATAC-Seq]

Project description:Transcription factor Etv6 controls functional differentiation of cross-presenting classical dendritic cells [ATAC-Seq]

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Transcription factor Etv6 controls functional differentiation of cross-presenting classical dendritic cells [ATAC-Seq]

Project description:An IRF8-dependent subset of classical dendritic cells (cDCs), termed DC1, effectively cross-primes CD8+ T cells and facilitates antitumor T cell responses. Etv6 is an ETS family transcription factor that controls hematopoietic stem and progenitor cell (HSPC) function. We report that like HSPC, cDCs express Etv6 but not its antagonist ETS1, whereas interferon-producing plasmacytoid dendritic cells (pDCs) express both factors. Deletion of Etv6 in the bone marrow reduced the generation of DC1-like cells in vitro and the differentiation of DC1 in vivo, including the loss of signature marker CD8a. Global expression and chromatin profiling of Etv6-deficient DCs revealed impaired lineage identity of DC1, including the reduction of cDC signature and upregulation of pDC signature. Accordingly, DC-specific Etv6 deletion impaired CD8+ T cell cross-priming and tumor-specific CD8+ T cell responses. These results identify Etv6 as a regulator of DC1 differentiation and functional fitness that indirectly facilitates T cell cross-priming and antitumor immunity.

2018-08-03 | GSE106405 | GEO

Transcription factor Etv6 controls functional differentiation of cross-presenting classical dendritic cells [RNA-Seq]

2018-08-03 | GSE106406 | GEO

Antigen Presenting Dendritic Cells

Project description:Assessing the gene expression repertoire of antigen presenting dendritic cells Keywords: other

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Expression data from mouse bone marrow myeloid dendritic cells (classical DCs) and classical dendritic cells in spleen

Project description:Classical dendritic cells may be found in mouse bone marrow and spleen. Due to the differences in their local environment, two populations may express different genes and potentially carry different functions We used microarrays to compare the gene expression profiles between myeloid dendritic cells and classical dendritic cells in spleen. Our data supported the hypothesis that bone marrow myeloid dendritic cells are enriched for the expression of certain sets of genes that may play specific functions in the bone marrow microenvironment

2018-03-21 | GSE112082 | GEO

Perforin-2 is a pore-forming effector of endocytic escape in cross-presenting dendritic cells

Project description:This study searched for cell-type specific effectors of endocytic escape in dendritic cells and identified a pore-forming protein, perforin-2 (encoded by Mpeg1), as a dedicated effector exclusive to cross-presenting cells. Whole cell proteomics identified differences in the abundance of tryptic and semi-tryptic (cleaved) perforin-2 peptides between control MutuDCs and cells treated with BafA, CpG or with knockout of asparagine endopeptidase (AEP). This revealed how perforin-2 undergoes proteolytic cleavage releasing its pore forming domain into the organellar lumen.

2023-06-27 | PXD041861 | Pride

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