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SRP145576
Saccharomyces cerevisiae
9 Downloadable Samples
Illumina HiSeq 2000
Description
The cysteine-rich PLAC8 domain occurs in proteins found in the majority of Eukaryotes. PLAC8-containing proteins play important yet diverse roles in different organisms, such as control of cell proliferation in animals and plants or heavy metals resistance in plants and fungi. For example, Onzin from Mus musculus is a key regulator of cell proliferation, whereas FCR1 from the ascomycete Oidiodendron maius is involved in cadmium resistance. We compared these two PLAC8-containing proteins by heterologous expression in the PLAC8-free yeast Saccharomyces cerevisiae in order to identify possible common functions. When expressed in yeast, both Onzin and FCR1 improved yeast cadmium resistance, reduced cadmium-induced DNA mutagenesis, localized in the nucleus and induced similar transcriptional changes. Our results support the hypothesis of a common ancestral function of the PLAC8 domain that may link Fe-S cluster biogenesis, iron homeostasis and the control of DNA damage, thus opening new perspectives to understand the role of this protein domain in the cellular biology of eukaryotes.
Publication Title
No associated publication
Alternate Accession IDs
None
Sample Metadata Fields
Specimen part, Disease, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA-seq analysis of 6 WHO grade-II tumors (n=4 with the rs55705857 genotype A/G and n=2 with the genotype A/A) that were IDH1-R132H mutant, 1p/19q co-deleted and ATRX-wild-type.
Publication Title
No associated publication
Alternate Accession IDs
None
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Race
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
The project investigated the role of Leucine-rich a2-glycoprotein 1 (LRG1) in the vascularization, immunogenicity and growth of B16F0 subcutaneous tumours in Control and LRG1 global knock out mice.
Publication Title
No associated publication
Alternate Accession IDs
None
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Cell line
View Samples- Homo sapiens
- 186 Downloadable Samples
Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 186 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Macrophage activation is associated with profound transcriptional reprogramming. Although much progress has been made in the understanding of macrophage activation, polarization and function, the transcriptional programs regulating these processes remain poorly characterized. We stimulated human macrophages with diverse activation signals, acquiring a dataset of 299 macrophage transcriptomes. Analysis of this dataset revealed a spectrum of macrophage activation states extending the current M1 versus M2-polarization model. Network analyses identified central transcriptional regulators associated with all macrophage activation complemented by regulators related to stimulus-specific programs. Applying these transcriptional programs to human alveolar macrophages from smokers and patients with chronic obstructive pulmonary disease (COPD) revealed an unexpected loss of inflammatory signatures in COPD patients. Finally, by integrating murine data from the ImmGen project we propose a refined, activation-independent core signature for human and murine macrophages. This resource serves as a framework for future research into regulation of macrophage activation in health and disease.
Publication Title
Transcriptome-based network analysis reveals a spectrum model of human macrophage activation.
Alternate Accession IDs
Sample Metadata Fields
Subject, Time
View Samples- Homo sapiens
- 51 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 22 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Regulatory T (Treg) cells are involved in self tolerance, immune homeostasis, prevention of autoimmunity, and suppression of immunity to pathogens or tumours. The forkhead transcription factor FOXP3 is essential for Treg cell development and function as mutations in FOXP3 cause severe autoimmunity in mice and humans. However, the FOXP3-dependent molecular mechanisms leading to this severe phenotype are not well understood. Here we introduce the chromatin remodelling enzyme SATB1 (special AT-rich sequence-binding protein-1) as an important target gene of FOXP3. So far, SATB1 has been associated with normal thymic T-cell development, peripheral T-cell homeostasis, TH1/TH2 polarization, and reprogramming of gene expression. In natural and induced murine and human FOXP3+ Treg cells SATB1 expression is significantly reduced. While there is no differential epigenetic regulation of the SATB1 locus between Treg and Teffector cells, FOXP3 reduces SATB1 expression directly as a transcriptional repressor at the SATB1 locus and indirectly via miR-155 induction, which specifically binds to the 3UTR of the SATB1 mRNA. Reduced SATB1 expression in FOXP3+ cells achieved either by overexpression or induction of FOXP3 is linked to significant reduction in TH1 and TH2 cytokines, while loss of FOXP3 function either by knock down or genetic mutation leads to significant upregulation of SATB1 and subsequent cytokine production. Alltogether, these findings demonstrate that reduced SATB1 expression in Treg cells is necessary for maintenance of a Treg-cell phenotype in vitro and in vivo and places SATB1-mediated T cell-specific modulation of global chromatin remodelling central during the decision process between effector and regulatory T-cell function.
Publication Title
Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation.
Alternate Accession IDs
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 51 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Whole transcriptome profiling (Illumina Microarray) of human ex vivo lymphocytes and monocytes, as well as of human monocyte-derived cells generated in vitro by activating CD14+ monocytes with MCSF, GMCSF or the combination of GMCSF and IL4
Publication Title
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Based on studies in knockout mice, several inhibitory factors such as TGF-beta, IL-10, or CTLA-4 have been implicated as gate keepers of adaptive immune responses. Lack of these inhibitory molecules leads to massive inflammatory responses mainly mediated by activated T cells. In humans, the integration of these inhibitory signals for keeping T cells at a resting state is less well understood. To elucidate this regulatory network we assessed early genome-wide transcriptional changes during serum deprivation in human mature CD4+ T cells. The most striking observation was a "TGF-beta loss signature" defined by downregulation of many known TGF-beta target genes. Moreover, numerous novel TGF-beta target genes were identified that are under the suppressive control of TGF-beta. Expression of these genes was upregulated once TGF-beta signaling was lost during serum deprivation and again suppressed upon TGF-beta reconstitution. Constitutive TGF-beta signaling was corroborated by demonstrating phosphorylated SMAD2/3 in resting human CD4+ T cells in situ, which were dephosphorylated during serum deprivation and re-phosphorylated by minute amounts of TGF-beta. Loss of TGF-beta signaling was particularly important for T cell proliferation induced by low-level T cell receptor and costimulatory signals. We suggest TGF-beta to be the most prominent factor actively keeping human CD4+ T cells at a resting state.
Publication Title
Human resting CD4+ T cells are constitutively inhibited by TGF beta under steady-state conditions.
Alternate Accession IDs
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Background: Development of target specific therapeutics greatly benefits from simultaneous identification of biomarkers to determine aspects of bioactivity, drug safety and efficacy or even treatment outcome. This is particularly important when targeting pleiotropic factors such as the TGFbeta system. TGFbeta has become a prime target for cancer therapeutics since inhibition of TGFbeta signaling simultaneously attacks the tumor and its microenvironment. Methods: Here we introduce blood transcriptomics followed by a defined set of validation assays as a promising approach to identify novel biomarkers for monitoring TGFbeta therapy. Findings: Our initial genome-wide analysis of transcription in peripheral blood revealed 12 candidate genes specifically regulated in peripheral blood by the TGFbeta receptor I kinase inhibitor LY2109761. In subsequent in vitro and in vivo molecular and immunological analyses, the combined monitoring of gene regulation of three genes, namely TMEPAI, OCIAD2, and SMAD7 was established as novel biomarkers for anti-TGFbeta based therapies. Interpretation: Overall, the proposed algorithm of biomarker identification is easily adapted towards other drug candidates for which gene regulation can be established in peripheral blood.
Publication Title
Application of T cell-based transcriptomics to identify three candidate biomarkers for monitoring anti-TGFbetaR therapy.
Alternate Accession IDs
Sample Metadata Fields
Specimen part
View Samples