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SRP155973
Mus musculus
10 Downloadable Samples
Illumina HiSeq 2500
Description
The transcription factor Helios is expressed in a large subset of Foxp3+ Tregs of both mouse and man. We previously demonstrated that Treg induced in peripheral sites (pTreg) from Foxp3- T conventional (Tconv) cells were Helios- and proposed that Helios is a marker of thymic derived Treg (tTreg). To compare the two Treg subpopulations, we generated Helios-GFP reporter mice and crossed them to Foxp3-RFP reporter mice. The Helios+ Treg population expressed a more activated phenotype and had a higher suppressive capacity in vitro. Both populations expressed a highly demethylated TSDR and both subsets were equivalent in their ability to suppress inflammatory bowel disease in vivo. However, Helios+ Treg more effectively inhibited the proliferation of activated, autoreactive splenocytes from scurfy mice. When Helios+ and Helios- Treg were transferred to lymphoreplete mice, both populations maintained comparable Foxp3 expression, but Foxp3 expression was less stable in Helios- Treg when transferred to lymphopenic mice. Gene expression profiling of the two populations demonstrated a large number of differentially expressed genes and that Helios- Treg subpopulation expressed certain genes normally expressed in CD4+Foxp3- T cells. TCR repertoire analysis indicated very little overlap between Helios+ and Helios- Treg. Thus, Helios+ and Helios- Treg subpopulations are phenotypically and functionally distinct, consistent with thymic and peripheral sites of origin, respectively. Because of their superior suppressive activity and enhanced stability Foxp3+Helios+ Treg represent the optimal Treg population for cellular immunotherapy. Overall design: 5 replicates of wildtype vs knockout Helios gene in Treg cells.
Publication Title
Helios<sup>+</sup> and Helios<sup>-</sup> Treg subpopulations are phenotypically and functionally distinct and express dissimilar TCR repertoires.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
- Illumina HiSeq 4000
Description
CD47 is a ubiquitous cell surface receptor that limits cell clearance by phagocytes that express its counter-receptor signal-regulatory protein-a and directly regulates T cell immunity by interacting with its inhibitory ligand thrombospondin-1. Murine natural killer (NK) cells express higher levels of CD47 than other lymphocytes, but the role of CD47 in regulating NK cell homeostasis and immune function remains unclear. Cd47-/- mice exhibited depletion of NK precursors in bone marrow, but antisense Cd47 knockdown or gene disruption resulted in a dose dependent accumulation of immature and mature NK cells in spleen. Cd47-/- mice were impaired in controlling chronic Clone-13 lymphocytic choriomeningitis virus (LCMV) infection, which was associated with depletion of splenic NK cells and loss of effector cytokine and interferon response gene expression in Cd47-/- NK cells. These data identify CD47 as a cell-intrinsic and systemic regulator of NK cell homeostasis and NK cell responses to viral infection. Overall design: Examining natural killer (NK) cell intrinsic role of CD47 during viral infection.
Publication Title
CD47 Expression in Natural Killer Cells Regulates Homeostasis and Modulates Immune Response to Lymphocytic Choriomeningitis Virus.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Illumina HiSeq 2500
Description
Regulatory T cells (Tregs) play a cardinal role in the immune system by suppressing detrimental autoimmune responses, but their role in acute and chronic infectious diseases remains unclear. We recently demonstrated that IFN-??? receptor (IFNAR) signaling promotes Treg function in autoimmunity. To dissect the functional role of IFNAR-signaling in Tregs during acute and chronic viral infection, we infected Treg-specific IFNAR deficient (IFNARfl/flxFoxp3YFP-Cre) mice with LCMV Armstrong and Clone-13. In both models, IFNARfl/flxFoxp3YFP-Cre mice Tregs expressed enhanced expression of Treg associated activation antigens. The enhanced activated phenotype was also seen when we compared the transcriptomes of IFNARfl/flxFoxp3YFP-Cre and wild type (WT) Tregs by RNA-Seq on day 25-post Clone-13 infection. LCMV-specific CD8+ T cells from IFNARfl/flxFoxp3YFP-Cre mice produced less antiviral IFN? and TNF? in both acute and chronic LCMV. In the chronic model, the numbers of anti-viral effector and memory CD8+ T cells were decreased in IFNARfl/flxFoxp3YFP-Cre mice and the effector CD4+ and CD8+ T cells exhibited a phenotype compatible with enhanced exhaustion. IFNARfl/flxFoxp3YFP-Cre mice cleared Armstrong infection normally, but had higher viral titers in sera, kidneys and lungs than WT mice during chronic infection. Thus, type I IFN signaling in Tregs is context-dependent, resulting in enhanced suppressor function in some models of autoimmunity, but decreased suppressor function in acute and chronic viral infection. Overall design: mRNA from Treg cells from 5 WT and 5 IFNAR deficient mice were analyzied by RNA-seq using Illumina HiSeq
Publication Title
Type I interferon signaling attenuates regulatory T cell function in viral infection and in the tumor microenvironment.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
CD4+ T cell differentiation into multiple T helper lineages is critical for optimal adaptive immune responses. This report identified a novel intrinsic mechanism by which PD-1 signaling imparted regulatory phenotype to FoxP3+ Th1 cells (denoted as Tbet+iTregPDL1 cells) and iTregs. Tbet+iTregPDL1 cells were capable of preventing inflammation in murine models of experimental colitis and experimental graft versus host disease. PDL-1 binding to PD-1 imparted regulatory function to Tbet+iTregPDL1 cells and iTregs by specifically downregulating an endolysosomal protease asparaginyl endopeptidase (AEP)
Publication Title
PD-1 Inhibitory Receptor Downregulates Asparaginyl Endopeptidase and Maintains Foxp3 Transcription Factor Stability in Induced Regulatory T Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 44 Downloadable Samples
- Illumina HiSeq 2000
Description
The complete transcriptomes of kidney cortex from 3 ?-HIF2aM3 18 month old TG+ male mice and 3 age matched wild type (WT) C57BL/6 male mice were sequenced on an Illumina HiSeq2000 Sequencer. Overall design: Examination of complete transcriptome of kidney cortex between ?-HIF2aM3 TG+ male mice and wild type C57BL/6 male mice
Publication Title
Activation of HIF2α in kidney proximal tubule cells causes abnormal glycogen deposition but not tumorigenesis.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Chronic alcohol consumption can lead to alchohol-related brain damage (ARBD). Despite the well known acute effects of alcohol the mechanism responsible for chronic brain damage is largely unknown. Pathologically the major change is the loss of white matter while neuronal loss is mild and restricted to a few areas such as the prefrontal cortex. In order to improve our understanding of ARBD pathogenesis we used microarrays to explore the white matter transcriptome of alcoholics and controls.
Publication Title
Comorbidities, confounders, and the white matter transcriptome in chronic alcoholism.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Danio rerio
- 9 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
In gastrulation, distinct progenitor cell populations are induced and sorted into the three germ layers ectoderm, mesoderm and endoderm. In order to identify genes involved in germ layer specification and morphogenesis, we identified genes differentially expressed between ectodermal and mesendodermal progenitor cells. To do so, we first generated highly enriched pools of ectodermal and mesendodermal progenitor cells. Mesendodermal cells were generated by over-expressing the Nodal signal Cyclops in wild type embryos and ectodermal cells were taken from mz-one-eyed-pinhead (oep) mutant embryos. We then compared the transcriptome of ectodermal versus mesendodermal cells taken from embryos at 7 hours post fertilization (hpf). In wild type embryos at this stage (70% epiboly), the first ectodermal and mesendodermal progenitor cells have already been sorted into their respective germ layers and ingression of mesendodermal progenitors is still ongoing.
Publication Title
Identification of regulators of germ layer morphogenesis using proteomics in zebrafish.
Sample Metadata Fields
Age, Specimen part, Subject, Time
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Damage-associated molecular pattern (DAMP) molecules S100A8 and S100A9 with well-known functions in inflammation, tumor growth and metastasis. It has been found to have promote tumor cell proliferation activity at low concentration . However, the mechanism underlying this remains unclear. In the current study, we performed genome expression profiling analysis using the Affymetrix genome wide microarray system to identify broad scale changes in gene expression associated with S100a8 or S100a9 recombinant protein stimulation in murine colon carcinoma cell line CT26.WT.
Publication Title
Inflammation-induced S100A8 activates Id3 and promotes colorectal tumorigenesis.
Sample Metadata Fields
Cell line
View Samples- Danio rerio
- 20 Downloadable Samples
- IlluminaHiSeq2500
Description
In this report, we have found that gata1 expressing erythroid cells contribute to a significant proportion of total body oxidative stress when animals were exposed to a strong pro-oxidant. RNA-seq of zebrafish under oxidative stress revealed the induction of tp53. Zebrafish carrying tp53 with mutation in its DNA binding domain were acutely sensitive to pro-oxidant exposure and displayed significant reactive oxygen species (ROS) and tp53-independent erythroid cell death resulting in an edematous phenotype. We found that a major contributing factor to ROS was increased basal mitochondrial respiratory rate without reserve. These data add to the concept that tp53, while classically a tumor suppressor and cell cycle regulator, has additional roles in controlling cellular oxidative stress. Overall design: We performed RNA-seq in two experiments. (1) Wild-type zebrafish embryos were exposed to 1-naphthol (vs no exposure) from 24 - 72 hpf (n = 5/group). (2) tp53 mutant zebrafish embryos were exposed to 1-naphthol (vs no exposure) from 24 - 72 hpf (n = 5/group).
Publication Title
TP53 Modulates Oxidative Stress in Gata1<sup>+</sup> Erythroid Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
The intestinal epithelium constitutes a crucial defense to the potentially life-threatening effects of gut microbiota. However, due to a complex underlying vasculature, hypoperfusion and resultant tissue ischemia pose a particular risk to function and integrity of the epithelium. The small ubiquitin-like modifier (SUMO) conjugation pathway critically regulates adaptive responses to metabolic stress and is of particular significance in the gut, as inducible knockout of the SUMO-conjugating enzyme Ubc9 results in rapid intestinal epithelial disintegration. Here we analyzed the pattern of individual SUMO isoforms in intestinal epithelium and investigated their roles in intestinal ischemia/reperfusion (I/R) damage. Immunostaining revealed that epithelial SUMO2/3 expression was almost exclusively limited to crypt epithelial nuclei in unchallenged mice. However, intestinal I/R or overexpression of Ubc9 caused a remarkable enhancement of epithelial SUMO2/3 staining along the crypt-villus axis. Unexpectedly, a similar pattern was found in SUMO1 knockout mice. Ubc9 transgenic mice, but also SUMO1 knockout mice were protected from I/R injury as evidenced by better preserved barrier function and blunted inflammatory responses. PCR array analysis of microdissected villus-tip epithelia revealed a specific epithelial contribution to reduced inflammatory responses in Ubc9 transgenic mice, as key chemotactic signaling molecules such as IL17A were significantly downregulated. Together, our data indicate a critical role particularly of the SUMO2/3 isoforms in modulating responses to I/R and provide the first evidence that SUMO1 deletion activates a compensatory process that protects from ischemic damage.
Publication Title
Ubc9 overexpression and SUMO1 deficiency blunt inflammation after intestinal ischemia/reperfusion.
Sample Metadata Fields
Treatment
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