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SRP132229
Mus musculus
6 Downloadable Samples
Illumina HiSeq 2000
Description
Blimp-1 expression in T cells extinguishes the T follicular helper cell fate and drives terminal differentiation, but also limits autoimmunity. Although various factors have been described to control Blimp-1 expression in T cells, little is known about what regulates Blimp-1 expression in Th2 cells and the molecular basis of its actions. Herein, we report that STAT3 unexpectedly played a critical role in regulating Blimp-1 in Th2 cells. Furthermore, we found that the cytokine IL-10 acted directly on Th2 cells and was necessary and sufficient to induce optimal Blimp-1 expression through STAT3. Together, Blimp-1 and STAT3 amplified IL-10 production in Th2 cells, creating a strong autoregulatory loop that enhanced Blimp-1 expression. Increased Blimp-1 in T cells antagonized STAT5-regulated cell cycle and anti-apoptotic genes to limit cell expansion. These data elucidate the signals required for Blimp-1 expression in Th2 cells and reveal an unexpected mechanism of action of IL-10 in T cells, providing insights into the molecular underpinning by which Blimp-1 constrains T cell expansion to limit autoimmunity. Overall design: RNAseq of activated undifferentiated CD4 T cells with or without exogenous expression of Blimp-1.
Publication Title
IL-10 induces a STAT3-dependent autoregulatory loop in T<sub>H</sub>2 cells that promotes Blimp-1 restriction of cell expansion via antagonism of STAT5 target genes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 322 Downloadable Samples
- IlluminaHiSeq2000
Description
We report the global pattern of ileal gene expression in a cohort of 359 treatment-naïve pediatric Crohn Disease, Ulcerative Colitis patients and controls. We focus on genes with consistent altered expression in inflamed and unaffected ileum of CD [ileal-involved CD (iCD) and non-invloved ileal CD (cCD)], but not in the ileum of ulcerative colitis or control. Overall design: Ileal biopsies were obtained during diagnostic colonoscopies of children and adolescents aged less than 17 years, who presented with IBD-like symptoms. All patients underwent baseline colonoscopy and histological characterization; non-IBD controls were those with suspected IBD, but with no microscopic or macroscopic inflammation and normal radiographic, endoscopic, and histologic findings. Biopsies were stored at -80 degrees.
Publication Title
Defining the Celiac Disease Transcriptome using Clinical Pathology Specimens Reveals Biologic Pathways and Supports Diagnosis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
Sample Metadata Fields
Sex, Age, Cell line, Treatment
View Samples- Oryza sativa
- 24 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
In response to bacterial infection, early transcriptional re-programming occurs in the host plant.
Publication Title
Antagonistic, overlapping and distinct responses to biotic stress in rice (Oryza sativa) and interactions with abiotic stress.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
Transcriptomes of mouse embryonic autopods were generated detecting expression of approximately 26179 transcripts in the developing forelimb or hindlimb autopods, representing about 58 % of the probe sets on MOE-430 A/B GeneChip. Three biological replicate array experiments were finished for each condition and MAS5.0 signal were used to do data analysis. Forty-four transcripts with expression differences higher than 2-fold were detected(T test, P<0.05), including Tbx4, Tbx5, Hoxc10 and Pitx1 which were previously shown to be differentially expressed in developing forelimb and hindlimb bud by in situ hybridization and SAGE study (Margulies 2001). RTPCR and in situ experiments confirmed several top differentially expressed genes which were newly discovered by our experiments. Vast amount of transcripts and its family members such as Bmp, Fgf, Epha, Wnt, T-box and Hox families detected to be highly expressed or differentially expressed in developing autopods, suggesting that the complexity of transcriptomes of developing autopods and dynamic differential expression and differential combinations of gene expression signals in the developing limb tissue contributes to differences in forelimb versus hindlimb patterning. The differentially expressed genes are the essential factors for morphological diversification of developing limb structures.
Publication Title
Transcriptome analysis of the murine forelimb and hindlimb autopod.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Circulating microRNAs (miRNA) are relatively stable in plasma and are a new class of disease biomarkers. Here we present evidence that human high-density lipoprotein (HDL) transports endogenous miRNAs and delivers them to recipient cells with functional targeting capabilities. Highly-purified fractions of human HDL contain small RNAs, and the HDL-miRNA profile from normal subjects is significantly different than familial hypercholesterolemia subjects. miRNAs were demonstrated to associate with both native and reconstituted HDL particles, and reconstituted HDL injected into mice retrieved distinct miRNA profiles from normal and atherogenic models. Cellular export of miRNAs to HDL was demonstrated to be regulated by neutral sphingomyelinase. HDL-mediated delivery of miRNAs to recipient cells was demonstrated to be scavenger receptor BI-dependent. Furthermore, HDL delivery of both exogenous and endogenous miRNAs resulted in the direct targeting of mRNA reporters. Notably, HDL-miRNA from atherosclerotic subjects induced differential gene expression, with significant loss of conserved mRNA targets in cultured hepatocytes. Collectively, these observations suggest that HDL participates in a novel mechanism of intercellular communication involving the transport and delivery of miRNAs.
Publication Title
MicroRNAs are transported in plasma and delivered to recipient cells by high-density lipoproteins.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
Here, we present a systematic and quantitative test of the hypothesis that the composition and activities of the endoplasmic reticulum (ER) proteostasis network impact mutational tolerance of secretory pathway client proteins. We focus on influenza hemagluttinin (HA), a viral coat protein that folds in the host's ER via a complex but well-characterized pathway. By integrating chemical methods to modulate the unfolded protein response with deep mutational scanning to assess mutational tolerance, we discover that upregulation of ER chaperones broadly enhances HA mutational tolerance across numerous sites and secondary/tertiary structure elements, including sites targeted by host antibodies. Remarkably, this host chaperone-enhanced mutational tolerance is observed at the same HA sites where mutational tolerance is most reduced by propagation at a fever-like temperature. Thus, host ER proteostasis mechanisms and temperature modulate HA mutational tolerance in opposite directions. This finding has important implications for influenza evolution, because influenza immune escape is contingent on HA possessing sufficient mutational tolerance to acquire antibody resistance while still maintaining the capacity to fold and function. More broadly, this work provides the first experimental evidence that the composition and activities of the ER proteostasis network critically define the mutational tolerance and, therefore, the evolution of secretory pathway client proteins. Overall design: RNA-seq characterizing a clonal HEK293T-Rex cell line, expressing DHFR ATF6f, Tet XBP1s, and the tetracycline repressor. These cell lines were treated with small molecules for 24 hours (in triplicate) to modulate the proteostasis environment in a stress-independent manner, at either 37C or 39C. XBP1s was activated by treatment with 0.1 ug/mL Doxycycline; ATF6f/XBP1s were activated by treatment with 0.1 ug/mL Doxycycline and 1 uM TMP; basal cells were vehicle-treated (0.01% DMSO). These cells were previously characterized in Shoulders et al. Cell Reports, 2013.
Publication Title
Enhanced ER proteostasis and temperature differentially impact the mutational tolerance of influenza hemagglutinin.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
We describe the preparation, evaluation, and application of an S100A12 protein-conjugated solid support, hereafter the “A12-resin,” that can remove 99% of Zn(II) from complex biological solutions without significantly perturbing the concentrations of other metal ions. The A12-resin can be applied to selectively deplete Zn(II) from diverse tissue culture media and from other biological fluids including human sera. To further demonstrate the utility of this approach, we investigated metabolic, transcriptomic, and metallomic responses of HEK293T cells cultured in medium depleted of Zn(II) using S100A12. Our data indicate that dividing cells can maintain a constant pool of free Zn(II), even under conditions of severe Zn(II) deprivation. We expect that the A12-resin will facilitate interrogation of disrupted Zn(II) homeostasis in biological settings, uncovering novel roles for Zn(II) in biology. Overall design: Defining the response of a cell line to Zn(II) starvation
Publication Title
A Method for Selective Depletion of Zn(II) Ions from Complex Biological Media and Evaluation of Cellular Consequences of Zn(II) Deficiency.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aging is associated with mitochondrial dysfunction and insulin resistance. We conducted a study to determine the role of long-term vigorous endurance exercise on age-related changes in insulin sensitivity and various indices of mitochondrial functions.
Publication Title
Endurance exercise as a countermeasure for aging.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Stress-independent activation of XBP1s and/or ATF6 reveals three functionally diverse ER proteostasis environments.
Sample Metadata Fields
Specimen part, Treatment
View Samples