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SRP156606
Mus musculus
12 Downloadable Samples
NextSeq 500
Description
Purpose: The goal of this study is to compare the transcriptional phenotype of lymphoid and kidney-infiltrating T cell populations in the setting of systemic inflammatory disease to determine how tissue location alters their phenotype. Methods: mRNA profiles of T cells isolated from 23-week-old nephritic (protein score of 3+ on dipstick) mice were used in this study. T cells were isolated by flow cytometry gated on CD45+Thy1.1+CD44+ and either CD4 or CD8+ T cells. RNA was isolated using the RNeasy Plus Micro Kit (Qiagen). Samples were sequenced using Illumina NextSeq 500 with 75bp paired-end reads and aligned to the mm10 genome using the STAR aligner. The number of uniquely aligned reads ranged from 10 to 12 million. Using an optimized data analysis workflow, Gene-level counts were determined using featureCounts and raw counts were analyzed for differential expression using the “voom” method in the “limma” R package. Results: After determining genes that were differentially expressed between splenic T cells and KIT, we performed gene set enrichment analysis (GSEA. Differentially expressed genes were compared to several previously defined gene signatures that are characteristic of CD8+ and CD4+ T cell exhaustion in the chronic LCMV infection model and tumor infiltrating lymphocytes. Genes from the CD8+ exhaustion cluster were significantly enriched among genes that were differentially expressed in CD8+ KITs vs CD8+ splenocytes. Overall design: mRNA profiles of CD4 and CD8 T cells from spleen and kidney of 23 week old wild MRL/lpr mice were generated in triplicate by sequencing using Illumina NextSeq 500
Publication Title
Kidney-infiltrating T cells in murine lupus nephritis are metabolically and functionally exhausted.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Hepatoblastoma (HB) is the most common pediatric liver tumor, and there are no targeted therapies available for children with HB. We have previously developed a murine model of HB which is driven by coactivation of the oncogenes YAP1 and -catenin (CTNNB1) [Tao J, Calvisi D, Ranganathan S, et al. Gastroenterology, 2014 Sep; 147(3): 690701]. We used the Sleeping Beauty transposase system combined with hydrodynamic tail vein injection to deliver plasmids containing mutant activated forms of YAP1 (YAP S127A) and -catenin (N90 -catenin) to a small number of pericentral hepatocytes. We have shown that these few transformed hepatocytes proliferate and dedifferentiate, eventually forming histologically heterogeneous tumors that resemble various subtypes of human HB (which is also highly heterogeneous), including areas of well-differentiated fetal, crowded fetal, embryonal, and blastemal HB. Our goal was to investigate how coactivation of YAP1 and -catenin drive the dedifferentiation of hepatocytes into hepatoblast-like tumor cells over time, leading to HB tumors. In order to measure changes in gene expression during tumorigenesis in our model, we used an Affymetrix microarray to analyze isolated RNA from wild type FVB mouse livers, mouse HB tumor tissue, and non-tumor liver tissue adjacent to HB tumors.
Publication Title
Hepatocyte-Derived Lipocalin 2 Is a Potential Serum Biomarker Reflecting Tumor Burden in Hepatoblastoma.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 150 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
An 8 hours timecourse was performed with human DCs infected either with A/California/7/2009 and A/Brevig Mission/1/1918 (pandemic) or A/New Caledonia/20/99 and A/Texas/36/91 seosonal.
Publication Title
Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 120 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
An 8 hours timecourse was performed with human DCs infected either with A/California/7/2009 and A/Brevig Mission/1/1918 (pandemic) or A/New Caledonia/20/99 and A/Texas/36/91 seosonal.
Publication Title
Human Dendritic Cell Response Signatures Distinguish 1918, Pandemic, and Seasonal H1N1 Influenza Viruses.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
HCT116 colon carcinoma cells invade more the basement membrane when carcinoma-associated fibroblasts (CAFs) are present. In order to identify if CAFs induce an invasive phenotype to HCT116 cells, and therefore regulate genes expression related to invasion, we compared gene expression of HCT116 cells cultured alone or in the presence of CAFs.
Publication Title
Cancer-associated fibroblasts induce metalloprotease-independent cancer cell invasion of the basement membrane.
Sample Metadata Fields
Disease, Cell line
View Samples- Mus musculus
- 38 Downloadable Samples
- NextSeq 500
Description
Regulatory T cells (Tregs) are a barrier to effective anti-tumor immunity. Neuropilin-1 (Nrp1) is required to maintain intratumoral Treg stability and function but is dispensable for peripheral immune homeostasis, Treg-restricted Nrp1 deletion in mice results in profound tumor resistant due to Treg functional fragility. Drivers of Treg fragility, the mechanistic basis of Nrp1 dependency, and the relevance of these processes for human cancer and immunotherapy remain unknown. NRP1 expression on human Tregs in melanoma and HNSCC was highly heterogeneous and correlated with prognosis. Using a mouse model of melanoma in which mutant Nrp1-deficient (Nrp1–/–) and wild type (WT) Tregs could be assessed in a competitive environment, we found that a high proportion of intratumoral Nrp1–/– Tregs produce interferon-? (IFN?), which in turn drove the fragility of surrounding WT Tregs, boosting anti-tumor immunity and facilitating tumor clearance. We also show that IFN?-induced Treg fragility is required for an effective response to PD1 immunotherapy, suggesting that cancer therapies promoting Treg fragility may be efficacious . Overall design: Tregs from B16 tumors and non-draining lymph nodes NDLN from WT, Nrp-1 deficient homozygous and heterozygous mice
Publication Title
Interferon-γ Drives T<sub>reg</sub> Fragility to Promote Anti-tumor Immunity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 90 Downloadable Samples
- NextSeq 500
Description
Regulatory T cells (T regs) maintain host self-tolerance but are a major barrier to effective cancer immunotherapy. T regs subvert beneficial anti-tumor immunity by modulating inhibitory receptor (IR) expression on tumor infiltrating lymphocytes (TILs); however, the underlying mediators and mechanisms remain elusive. Here we show that interleukin-10 (IL10) and interleukin-35 (IL35; Ebi3/IL12a heterodimer) are divergently expressed by T reg subpopulations in the tumor microenvironment (TME) and cooperatively promote intratumoral T cell exhaustion. T reg -restricted deletion of Il10 and/or Ebi3 resulted in delayed tumor growth, loss of multi-IR expression, and reduced intratumoral CD8 + T cell exhaustion signature. While Il10 or Ebi3 loss was associated with reduced expression of B lymphocyte-induced maturation protein-1 (BLIMP1; Prdm1), IL10 and IL35 differentially impacted effector versus memory T cell fates, respectively, highlighting their differential, partially overlapping but non-redundant regulation of anti-tumor immunity. Our results reveal previously unappreciated cooperative roles for IL10 and IL35, produced by limits effective anti-tumor immunity Overall design: TIL CD8 cells from Treg specific IL10, IL35 and double knockouts, sorted into populations based on exhaustion markers. TIL Tregs sorted based on IL10 and IL35 expression.
Publication Title
Adaptive plasticity of IL-10<sup>+</sup> and IL-35<sup>+</sup> T<sub>reg</sub> cells cooperatively promotes tumor T cell exhaustion.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- NextSeq 500
Description
Abstract: Regulatory T cells (Tregs) maintain host self-tolerance but are a major barrier to effective cancer immunotherapy. Tregs subvert beneficial anti-tumor immunity by modulating inhibitory receptor (IR) expression on tumor infiltrating lymphocytes (TILs); however, the underlying mediators and mechanisms remain elusive. Here we show that interleukin-10 (IL10) and interleukin-35 (IL35; a heterodimer of Ebi3 and IL12?) are reciprocally expressed by Treg-subpopulations in the tumor microenvironment (TME) and cooperatively promote intratumoral T cell exhaustion. Treg-restricted deletion of either Il10/Ebi3 or dual deletion resulted in delayed tumor growth and significant reduction of transcriptomic exhaustion signature associated with reduced expression of B lymphocyte-induced maturation protein-1 (BLIMP1; Prdm1). While the two cytokines share the BLIMP1 axis to drive multi-IR expression; they differentially impact effector vs. memory fate, highlighting their overlapping and non-redundant regulation of anti-tumor immunity. Our results reveal previously unappreciated adaptive plasticity in inhibitory cytokine expression pattern by Tregs in TME for maximal immunosuppression. Data purpose: to understand the segregated cytokine expression pattern and the preferential generation of single cytokine positive Treg subpopulations, we performed single cell RNASeq (scRNAseq) contrasting Tregs isolated from naïve, unchallenged LNs or day 14 B16 tumor from Foxp3Cre-YFP WT mice Overall design: LNs or day 14 B16 tumor from Foxp3Cre-YFP WT mice
Publication Title
Adaptive plasticity of IL-10<sup>+</sup> and IL-35<sup>+</sup> T<sub>reg</sub> cells cooperatively promotes tumor T cell exhaustion.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease.
Publication Title
Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification.
Sample Metadata Fields
Specimen part
View Samples