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The exonuclease TREX1 constitutes an innate immune checkpoint limiting cGAS/STING-mediated anti- tumor immunity

ABSTRACT: Given that TREX1-deficient tumor cells showed a growth delay in immunocompetent but not immunodeficient hosts, we characterize the consequences of CT26 tumor-intrinsic TREX1 loss on the host immune system by performing single-cell RNA sequencing on intra-tumoral immune cells sorted from control and TREX1 KO CT26 tumors.

INSTRUMENT(S): Illumina NovaSeq 6000

ORGANISM(S): Mus musculus

SUBMITTER:

PROVIDER: E-MTAB-13823 | biostudies-arrayexpress |

SECONDARY ACCESSION(S): E-MTAB-13815

REPOSITORIES: biostudies-arrayexpress

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CT26 sorted in vivo tumor cells with Trex1 KO

Project description:The DNA exonuclease TREX1 degrades endogenous cytosolic DNA. Cytosolic DNA triggers the cGAS/STING pathway which increases type I interferon. To investigate the physiological significance of TREX1 loss on in vivo tumor growth, we implanted control and TREX1-deficient CT26 tumor cells into immunocompetent BALB/c hosts.Tumor cells were collected 7 days after tumors reached around 200mm3.

2024-03-12 | E-MTAB-13816 | biostudies-arrayexpress

An IL-1β driven neutrophil-stromal cell axis fosters a BAFF-rich microenvironment in multiple myeloma

Project description:Neutrophils are the most abundant nucleated cell type in the bone marrow. A pro-tumor bias in this cell type may have implications for bone-marrow residing malignancies, such as multiple myeloma. Here, we generated single cell transcriptomic overviews of the entire myeloid compartment, including the entire neutrophilic lineage, of the bone marrow of 6 newly diagnosed myeloma patients, 5 treated myeloma patients and 4 non-cancer controls. We find dat mature neutrophils in myeloma patients, both newly diagnosed and treated, have an activated and pro-inflammatory phenotype, accompanied by increased transcription of pro-inflammatory cytokines, such as IL-1β, and myeloma cell survival factors, such as BCMA-ligand BAFF/TNFSF13B. Moreover, inflammatory stromal cells can activate naive neutrophils to acquire an inflammatory phenotype as is seen in patients. Previously, we have shown that inflammatory stromal cells characterized the bone marrow of newly diagnosed myeloma patients. Here, we generate single cell RNA sequencing dataset of non-hematopoietic bone marrow cells of patients after induction treatment, high-dose melphalan, stem cell transplantation and consolidation treatment. We show that this intensive treatment reduced, but did not normalize, stromal inflammation.

2023-03-31 | E-MTAB-12760 | biostudies-arrayexpress

Paired scRNAseq of the and non-hematopoietic and the immune microenvironment of aspirates from newly diagnosed Multiple Myeloma patients versus non-cancer controls

Project description:By generating a paired single cell RNA-sequencing database of the tumor niche from 10 newly diagnosed MM patients, we created a unique dataset allowing the in-depth analyses of stromal-immune interactions within the tumor microenvironment. Using this database, we identified the presence of inflammatory stromal fibroblasts in the bone marrow of Myeloma patients.The stromal inflammation was associated with NF-κB signaling, and sources of IL-1β or TNFα were specific immune subsets previously shown to be altered in MM, suggesting the presence of an immune cell-mediated feed-forward loop of bone marrow inflammation in MM. By tracking inflammatory signatures over time in individual patients undergoing first-line treatment using bulk RNA sequencing, we show that bone marrow inflammation is not reverted by successful anti-tumor therapy (see related accession number), suggesting a role for stromal fibroblasts and bone marrow inflammation in disease persistence or relapse.

2020-09-30 | E-MTAB-9139 | biostudies-arrayexpress

Aire secures the transcription of polycomb marked genes to complete a comprehensive program of promiscuous gene expression in the thymic epithelial cell lineage

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-09-04 | E-GEOD-53111 | biostudies-arrayexpress

RNA-Seq of Group 2 innate lymphoid cells (ILC2) from uterine tissue (Virgin, E9.5, E18.5)

Project description:Group 2 innate lymphoid cells (ILC2) promote the production of a type-2 immunological environment in the uterus and have tissue-specific gene signatures that change with pregnancy.

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RNA-Seq of Group 2 innate lymphoid cells (ILC2) from lung and lymph node

2023-04-15 | E-MTAB-5806 | biostudies-arrayexpress

Bulk RNAseq of control and 5TGM1 myeloma-bearing bone marrow T, NK, and non-hematopoietic stromal cells from C57Bl/6 mice

Project description:We hypothesized that the immune microenvironment of the bone marrow influences the progression of myeloma outgrowth in the 5TGM1 transfer model of multiple myeloma. Therefore we sorted bone marrow T, NK, and non-hematopoietic stromal cells from control and tumor-bearing C57Bl/6 mice.

2023-02-24 | E-MTAB-12615 | biostudies-arrayexpress

Gene expression in thymic epithelial cells [RNA-seq]

Project description:This study set out to assay the (polyA+) transcriptomes of specific FACS sorted populations of mouse thymic epithelial cells (TEC). Two biological replicates of each of seven murine TEC populations were FACS sorted and sequenced.

2014-09-04 | E-GEOD-53110 | biostudies-arrayexpress

Chromatin state in thymic epithelial cells [ChIP-seq]

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2014-09-04 | E-GEOD-53109 | biostudies-arrayexpress

scRNAseq of the bone marrow immune microenvironment in control and 5TGM1 myeloma-bearing C57Bl/6 and KaLwRij mice

Project description:We hypothesized that the immune microenvironment of the bone marrow influences the progression of myeloma outgrowth in the 5TGM1 transfer model of multiple myeloma. Therefore we sorted bone marrow T, B, NK, neutrophils, and monocytes/macrophages from control and tumor-bearing C57Bl/6 and KaLwRij mice.

2023-02-23 | E-MTAB-12616 | biostudies-arrayexpress

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