Single-cell analysis of mouse CD4 T cells with HDAC1 KO
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Illumina NovaSeq 6000
ORGANISM(S): Mus musculus
SUBMITTER: Johan Henriksson
PROVIDER: E-MTAB-13089 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Shared Molecules
Only show the datasets with similarity scores above: 0.5
Threshold
0.5
Similar Datasets
Project description:Although CD4 T cell senescence plays an important role in immunosenescence, the mechanisms remain unclear. We found that T cell-specific Menin deficiency results in the premature senescence of CD4 T cells, accompanied by the senescence-associated secretory phenotype (SASP) after antigenic stimulation. TH1 and TH2 differentiation was dysregulated in Menin-knockout CD4 T cells. Bach2, which regulates SASP and TH differentiation, was identified as a Menin target. Menin binds to the Bach2 locus, and controls its expression through maintenance of histone acetylation. These findings reveal a critical role of the Menin-Bach2 pathway in regulating CD4 T cell senescence and homeostasis, thus indicating the involvement of this pathway in the inhibition of age-associated development of inflammatory diseases, which are induced by immunosenescence. Examination of transcriptional factor Menin binding and histone modefications in Menin WT and KO CD4 T cells
2014-03-27 | E-GEOD-53831 | biostudies-arrayexpress
Project description:Differentiation of CD8+ T lymphocytes into effector and memory cells is key for an adequate immune response and relies on complex interplay of pathways that convey signals from cell surface to nucleus. In this study, we fractionated four CD8+ T cell subtypes; naïve, recently activated effector, effector and memory cells into membrane, cytosol, soluble nucleus, chromatin-bound and cytoskeleton compartments. Using LC-MS/MS analysis, identified peptides were matched to human peptides/proteins (SwissProt). Compartment fractionation and gel-LC-MS separation identified 2399 proteins in total. Among these 735 were detected in all five, 241 in four, 257 in three, 368 in two and 798 found in only one fraction. Comparison between the two most different subsets, naïve and effector, yielded 146 significantly regulated proteins.
2015-02-04 | PXD001065 | Pride
Project description:Background: A specific subset of regulatory IL-10 producing B cells has been extensively studied in autoimmune and inflammatory pathologies. These cells are able to constrain exacerbated inflammation by inhibiting T cell mediated responses and maturation of antigen presenting cells. In allergic diseases, observations that increase of regulatory B cells is necessary for allergen tolerance suggest that development of allergic asthma would be associated with a defect in the regulatory B cells compartment. Objective: We sought to (i) characterize regulatory IL-10+ regulatory B cell subset in Balb/c mice by microarray and flow cytometry and (ii) investigate their regulatory capacity in vivo in a house dust mite model of allergic asthma. Results: We identified an IL-10 producing B cells subset able to control T cell proliferation in vitro in both control and asthmatic mice. This subset is decreased in allergic mice. IL-10+ Breg cells express high levels of CD9 and upregulate CD70 and CD73 after activation. Expression of CD9 allows identifying more than 50% of Bregs. Interestingly CD9+ B cells inhibit TH2-TH17 allergic airway inflammation in vivo after adoptive transfer in an IL-10 dependent manner. Conclusions: Herein, we demonstrate that induction of allergic asthma dampens the generation of Bregs contributing to exacerbated airway inflammation. We identified a distinct CD9+ Breg-cell population decreased in lung of HDM mice and able to control asthma and allergic airway inflammation by producing IL-10 after adoptive transfer. This study points B cells as an interesting therapeutic target in allergic asthma. IL-10+ B cells (n=3) and 3 IL-10- B cells (n=3) in control mice + IL-10+ B cells (n=3) and 3 IL-10- B cells (n=3) from asthmatic allergic (HDM) mice
2015-03-01 | E-GEOD-57772 | biostudies-arrayexpress
Project description:BACKGROUND: Peroxisome proliferator-activated receptor g (PPAR g) is a nuclear receptor whose activation has been shown to modulate macrophage and epithelial cell-mediated inflammation. The objective of this study was to use a systems approach for investigating the mechanism by which the deletion of PPAR g in T cells modulates the severity of dextran-sodium sulfate (DSS)-induced colitis, immune cell distribution and global gene expression. METHODS: Wild-type (WT) or PPAR g flfl; CD4 Cre+ (CD4cre) mice in a C57BL/6 background were challenged with 2.5% DSS in their drinking water for 0, 2, or 7 days. Mice were scored on disease severity both clinically and histopathologically. Flow cytometry was used to assess lymphocyte and macrophage populations in the blood, spleen, and mesenteric lymph nodes (MLN). Global gene expression in colonic mucosa was profiled using Affymetrix microarrays. RESULTS: Both disease severity and inflammation-related body weight loss were accelerated by the deficiency of PPAR g in T cells. Examination of colon histopathology revealed significantly greater epithelial erosion, leukocyte infiltration, and mucosal thickening in the CD4cre mice on day 7. CD4cre mice had more CD8+ T cells than wt mice and fewer CD4+FoxP3+ regulatory T cells (Treg) and IL10+CD4+ T cells in blood and MLN, respectively. Transcriptomic profiling revealed around 3000 genes being transcriptionally altered as a result of DSS challenge in CD4cre mice. These included up-regulated adhesion molecules on day 7 and proinflammatory cytokines interleukin-6 (IL-6) and IL-1b, and suppressor of cytokine signaling 3 (SOCS-3) mRNA expression. CONCLUSIONS: These findings suggest that T cell PPAR g down-regulates inflammation during DSS colitis by inhibiting colonic expression of inflammatory mediators and increasing MLN Treg. Colonic mucosa from wt and CD4cre mice were sampled at 0 (no DSS), 2, and 7 days of DSS-induced experimental colitis
2010-07-08 | E-GEOD-20523 | biostudies-arrayexpress
Project description:This data is from a murine model established to study the lasting impact of allergic airway sensitization on subsequent anti-viral memory T cell responses and the ability to develop protective immunity to reinfection. Animals were either sensitised by exposure to HDM or PBS and then subsequently exposed to influenza virus. Samples were collected at various time points for analysis of both CD8 and C4 positive tissue resident memory T cells.
2023-01-30 | E-MTAB-11116 | biostudies-arrayexpress
Project description:Mouse Marginal Zone B-cell with/without Tfh
2024-01-24 | E-MTAB-11677 | biostudies-arrayexpress
Project description:This experiment compared the expression of mRNAs and noncoding RNAs between resting and activated CD8+ effector T cells, with the primary aim of identifying noncoding RNAs that were dynamically regulated during T cell activation.
2008-11-01 | E-TABM-491 | biostudies-arrayexpress
Project description:Background. Dyslipidemia is associated with chronic kidney disease (CKD). It has been shown that inhibition of β-oxidation and lipid accumulation are common threats in the onset of kidney injury and conducive to fibrosis. We characterized the S-acylated proteome of kidneys from mice with diet-induced nephropathy, to uncover novel lipid-related biochemical changes that might contribute to the lipid-induced kidney dysfunction. Methods. We conducted total and S-acylated proteomics, and lipidomics of the renal crude membrane fractions of mice fed a high-fat diet (HFD). Then, we investigated in vitro the effect of S-acylation inhibition on megalin expression and ligand binding. Results. HFD caused albuminuria with unchanged kidney function. The dietary intervention induced a large-scale repression of protein S-acylation as well as of the most abundant ceramides and sphingomyelin species, which are highly suggestive of an overall reduction in acyl-CoA availability. S-acylation repression mostly affected proteins involved in endocytosis and intracellular transport. In particular, the kidney of the mice fed a HFD, which are characterized by albuminuria, displayed a marked decrease in the total amount and in the S-acylated form of megalin, the main tubular protein retrieval system. Further in vitro experiments indicated that S-acylation is important for total expression of megalin. Conclusions. The diet-induced derangement of fatty acids metabolism modifies the renal landscape of the S-acylated proteome during early stage of the kidney injury, which might reduce the maximal capacity of protein reabsorption by the proximal tubule.
2025-03-21 | PXD052634 | Pride
Project description:Acute Pten loss initiates prostate tumorigenesis characterized by cellular senescence response. Here we examine the cellular senescence response in epithelial individual cells, by single-cell RNA sequencing (scRNAseq) in Ptenpc-/- and Ptenpc-/-; Timp1-/- GEMMs. ScRNAseq analysis determines a cluster of senescent cells expressing the senescence-related genes. A significant positive correlation is observed between the senescence score and Bcl2 expression. This provides the rational for targeting senescent cells using Bcl2 inhibitor.
2020-10-09 | E-MTAB-9578 | biostudies-arrayexpress
Project description:Histone deacetylase 1 and 2 (HDAC1/2) regulate chromatin structure as the catalytic core of the Sin3A, NuRD and CoREST co-repressor complexes. To better understand the key pathways regulated by HDAC1/2 in the adaptive immune system and inform their exploitation as drug targets, we have generated mice with a T cell specific deletion and performed comparative genomic hybridisation using genomic DNA from HDAC1-/-; HDAC2+/- diseased thymocytes and sample-matched, wild-type tail. A data set from a related transcription-profiling study comparing HDAC1-/-; HDAC2+/- mouse thymus tissue against thymus tissues from wild-type counterparts has also been deposited at ArrayExpress under accession E-MTAB-1432: http://www.ebi.ac.uk/arrayexpress/experiments/E-MTAB-1432
2013-01-08 | E-MTAB-1433 | biostudies-arrayexpress