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Homo sapiens
8 Downloadable Samples
Affymetrix Clariom S Pico Assay HT (clariomshumanht)
Description
Low-dose epirubicin at non-cytotoxic doses down regulated NLRP3 inflammasome components and reduced the release of proinflammatory cytokines.
Publication Title
Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
Histone deacetylase 3 (HDAC3) is the catalytic component of NCoR/SMRT corepressor complexes that mediate the actions of transcription factors implicated in the regulation of B cell development and function. We crossed Hdac3 conditional knockout mice with Mb1-Cre knockin animals to delete Hdac3 in early progenitor B cells. The spleens of Hdac3F/-Mb1-Cre+/- mice were virtually devoid of mature B cells, and B220+CD43+ B cell progenitors accumulated within the bone marrow. Quantitative deep sequencing of the immunoglobulin heavy chain locus from B220+CD43+ populations identified a defect in VHDJH recombination with a severe reduction in productive rearrangements, which directly corresponded to the loss of pre-B cells from Hdac3D/- bone marrow. For Hdac3D/- B cells that did show productive VDJ rearrangement, there was significant skewing toward the incorporation of proximal VH gene segments and a corresponding reduction in distal VH gene segment usage. While transcriptional effects within these loci were modest, Hdac3D/- progenitor cells displayed global changes in chromatin structure that likely hindered effective distal V-DJ recombination. Re-introduction of wild type Hdac3 restored normal B cell development, whereas an Hdac3 point mutant lacking deacetylase activity failed to complement this defect. Thus, the deacetylase activity of Hdac3 is required for the generation of mature B cells. Overall design: Bone marrow was isolated from Hdac3+/+Mb1cre+/- or Hdac3F/-Mb1cre+/- mice at 8 weeks of age. B220+CD43+ B cells were isolated from marrow by FACS and cells from two mice were pooled per sample. Total RNA isolated by Trizol extraction.
Publication Title
Deacetylase activity of histone deacetylase 3 is required for productive <i>VDJ</i> recombination and B-cell development.
Sample Metadata Fields
Specimen part, Cell line, Subject
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GSE73535- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Histone Deacetylase 3 Is Required for Efficient T Cell Development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Hdac3 is an important target of HDAC inhibitors used in the treatment of cutaneous T cell lymphoma. In order to gain an understanding of Hdac3 function in T cells,we deleted Hdac3 from early mouse thymocytes using LCK-Cre. Hdac3 deletion resulted in a loss of single positive thymocytes due to a defect in positive selection at the double positive (DP) stage of thymocyte development. To better characterize this defect, we sorted the DP1 and DP2 populations to for gene expression profiling. Overall design: Total RNA was extracted from DP1 (GFP+CD4+CD8+CD5loTCRblo) or DP2 (GFP+CD4+CD8+CD5hiTCRbint) thymocytes isolated by FACS from Hdac3+/+ or Hdac3F/F LCK-Cre+ animals. Libraries were constructed from rRNA-depleted total RNA pools to identify altered gene expression in DP populations following Hdac3 deletion.
Publication Title
Histone Deacetylase 3 Is Required for Efficient T Cell Development.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Histone deacetylase 9 (HDAC9) is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL). We examined HDAC9 protein expression and copy number alterations in primary B-NHL samples, identifying high HDAC9 expression among various lymphoma entities and HDAC9 copy number gains in 50% of diffuse large B-cell lymphoma (DLBCL). To study the role of HDAC9 in lymphomagenesis, we generated a genetically engineered mouse (GEM) model that constitutively expressed an HDAC9 transgene throughout B-cell development under the control of the immunoglobulin heavy chain (IgH) enhancer (E). Here, we report that the E-HDAC9 GEM model develops splenic marginal zone lymphoma and lymphoproliferative disease (LPD) with progression towards aggressive DLBCL, with gene expression profiling supporting a germinal center cell origin, as is also seen in human B-NHL tumors. Analysis of E-HDAC9 tumors suggested that HDAC9 might contribute to lymphomagenesis by altering pathways involved in growth and survival, as well as modulating BCL6 activity and p53 tumor suppressor function. Epigenetic modifications play an important role in the germinal center response, and deregulation of the B-cell epigenome as a consequence of mutations and other genomic aberrations are being increasingly recognized as important steps in the pathogenesis of a variety of B-cell lymphomas. A thorough mechanistic understanding of these alterations will inform the use of targeted therapies for these malignancies. These findings strongly suggest a role for HDAC9 in B-NHL and establish a novel GEM model for the study of lymphomagenesis and, potentially, preclinical testing of therapeutic approaches based on histone deacetylase inhibitors.
Publication Title
Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
B220+GL7+ (GC) and B220+GL7- (non-GC) B cells were sorted from SRBC-immunized mice deficient for Hdac3 and wild type controls. RNA-sequencing revealed an upregulation of critical regulators of B cell differentiation in Hdac3-deleted animals. Overall design: 10 days post-immunization with SRBCs, GC and non-GC B cells were sorted and RNA isolated by Trizol extraction for RNA-sequencing. 2 replicates were sequenced for each condition.
Publication Title
Germinal centre hypoxia and regulation of antibody qualities by a hypoxia response system.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Background: To define changes in gene expression from stem cells and early progenitor cells lacking histone deacetylase 3 (Hdac3), we purified bone marrow Lineage Negative, Sca1/cKit positive and Flt3 negative cells from wild type and Vav-Cre/Hdac3Flox/- mice. These lineage-specific knock out mice lack Hdac3 throughout the hematopoietic system. To ensure that only cells lacking Hdac3 were measured, we used a Lox-STOP-Lox-ROSA26-GFP transgene such that any cell containing active Cre also expresses GFP.
Publication Title
HDAC3 is essential for DNA replication in hematopoietic progenitor cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 47 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.
Publication Title
Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The immune mechanisms that control resistance vs. susceptibility to mycobacterial infection in humans were investigated by studying leprosy skin lesions, the site where the battle between the host and the pathogen is joined. Using an integrative genomics approach, we found an inverse correlation between of IFN-beta and IFN-gamma gene expression programs at the site of disease. The Type II IFN, IFN-gamma and its downstream vitamin D-dependent antimicrobial genes were preferentially expressed in the lesions from patients with the self-healing tuberculoid form of the disease and mediated antimicrobial activity against the pathogen, Mycobacterium leprae in vitro. In contrast, the Type I IFN, IFN-beta and its downstream genes, including IL-27 and IL-10, were induced in monocytes by M. leprae in vitro, and were preferentially expressed in the lesions of disseminated and progressive lepromatous form. The IFN-gamma induced macrophage antimicrobial response was inhibited by IFN-beta/IL-10, by a mechanism involving blocking the generation of bioactive 1,25-dihyroxy vitamin D as well as inhibiting induction of antimicrobial peptides cathelicidin and DEFB4. The ability of IFN-B to inhibit the IFN-gamma induced vitamin D pathway including antimicrobial activity was reversed by neutralization of IL-10, suggesting a possible target for therapeutic intervention. Finally, a common IFN-beta and IL-10 gene signature was identified in both the skin lesions of leprosy patients and in the peripheral blood of active tuberculosis patients. Together these data suggest that the ability of IFN-beta to downregulate protective IFN-gamma responses provides one general mechanism by which some bacterial pathogens of humans evade protective host responses and contribute to pathogenesis.
Publication Title
Type I interferon suppresses type II interferon-triggered human anti-mycobacterial responses.
Sample Metadata Fields
Specimen part, Subject
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