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SRP049523
Homo sapiens
7 Downloadable Samples
IlluminaHiSeq2000
Description
Some of the functions and mechanisms of PPAR?-mediated regulation of vascular homeostasis have been revealed, the potential role of PPAR? in angiogenesis is obscure. In human ECs, PPAR?-deficiency was studied using siRNA strategy and RNA sequencing was utilized to reveal angiogenesis-associated targets for PPARg. Overall design: Our aim is to reveal the possible role of PPARy in angiogenesis.
Publication Title
Loss of PPARγ in endothelial cells leads to impaired angiogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 53 Downloadable Samples
Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 42 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
CD8+ T cells in chronic viral infections like HIV develop functional defects such as loss of IL-2 secretion and decreased proliferative potential that are collectively termed exhaustion1. Exhausted T cells express increased levels of multiple inhibitory receptors, such as Programmed Death 1 (PD-1). PD-1 inhibition contributes to impaired virus-specific T cell function in chronic infection because antibody-mediated blockade of its ligand, Programmed Death Ligand 1 (PD-L1) is sufficient to improve T cell function and reduce viral replication in animal models. Reversing PD-1 inhibition is therefore an attractive therapeutic target, but the cellular mechanisms by which PD-1 ligation results in T cell inhibition are not fully understood. PD-1 is thought to limit T cell activation by attenuating T cell receptor (TCR) signaling. It is not known whether PD-1 ligation also acts by upregulating genes in exhausted T cells that impair their function. Here, we analyzed gene-expression profiles from HIV-specific CD8+ T cells in patients with HIV and show that PD-1 coordinately upregulates a program of genes in exhausted CD8+ T cells from humans and mice. This program includes upregulation of basic leucine transcription factor, ATF-like (BATF), a transcription factor in the AP-1 family. Enforced expression of BATF was sufficient to impair T cell proliferation and cytokine secretion, while BATF knockdown reduced PD-1 inhibition. Silencing BATF in CD4+ and CD8+ T cells from chronic viremic patients rescued HIV-specific T cell function. Thus inhibitory receptors can cause T cell exhaustion by upregulating genes such as BATF that inhibit T cell function.
Publication Title
Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
CD8+ T cells in chronic viral infections like HIV develop functional defects such as loss of IL-2 secretion and decreased proliferative potential that are collectively termed exhaustion1. Exhausted T cells express increased levels of multiple inhibitory receptors, such as Programmed Death 1 (PD-1). PD-1 inhibition contributes to impaired virus-specific T cell function in chronic infection because antibody-mediated blockade of its ligand, Programmed Death Ligand 1 (PD-L1) is sufficient to improve T cell function and reduce viral replication in animal models. Reversing PD-1 inhibition is therefore an attractive therapeutic target, but the cellular mechanisms by which PD-1 ligation results in T cell inhibition are not fully understood. PD-1 is thought to limit T cell activation by attenuating T cell receptor (TCR) signaling. It is not known whether PD-1 ligation also acts by upregulating genes in exhausted T cells that impair their function. Here, we analyzed gene-expression profiles from HIV-specific CD8+ T cells in patients with HIV and show that PD-1 coordinately upregulates a program of genes in exhausted CD8+ T cells from humans and mice. This program includes upregulation of basic leucine transcription factor, ATF-like (BATF), a transcription factor in the AP-1 family. Enforced expression of BATF was sufficient to impair T cell proliferation and cytokine secretion, while BATF knockdown reduced PD-1 inhibition. Silencing BATF in CD4+ and CD8+ T cells from chronic viremic patients rescued HIV-specific T cell function. Thus inhibitory receptors can cause T cell exhaustion by upregulating genes such as BATF that inhibit T cell function.
Publication Title
Transcriptional analysis of HIV-specific CD8+ T cells shows that PD-1 inhibits T cell function by upregulating BATF.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 35 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This experiment compares the transciptional changes in antigen specific murine CD8 T cells (P14 T cells) after exposure in vivo to dendritic cells (DC) pulsed with low dose cognate peptide (1uM KAVYNFATC), high dose cognate peptide (100uM KAVYNFATC) or no antigen. Splenic dendritic cells were freshly isolated, peptide pulsed, washed and then adoptively transferred s.c. to the right footpad of C57BL/6 hosts. After 18h, freshly isolated P14 CD8 T cells were labelled with CMFDA and adoptively transferred iv. Two hours after T cell transfer, anti-L selectin antibody was given iv. At 12 and 24 hours, recipients were sacrificed and The right popliteal LN was harvested at 12 or 24h post T cell transfer and a single cell suspension was created and stained with PE CD4, B220 and CD19 (dump channel). Cells were then sorted on a FacsARIA for being non-doublets, CMFDA positive and dump channel negative.
Publication Title
Antigen availability determines CD8⁺ T cell-dendritic cell interaction kinetics and memory fate decisions.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Exon 1.0 ST Array [CDF: huex10st_Hs_ENSG_20.0 (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 21 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Todays diagnostic tests for multiple myeloma (MM) reflect the criteria of the updated WHO classification based on biomarkers and clinicopathologic heterogeneity. To that end, we propose a new subtyping of myeloma plasma cells (PC) by B-cell subset associated gene signatures (BAGS), from the normal B-cell hierarchy in the bone marrow (BM). To do this, we combined FACS and GEP data from normal BM samples to generate classifiers by BAGS for the PreBI, PreBII, immature (Im), nave (N), memory (M) and PC subsets. The resultant tumor assignments in available clinical datasets exhibited similar BAGS subtype frequencies in four cohorts across 1302 individual cases. The prognostic impact of BAGS was analyzed in patients treated with high dose melphalan as first line therapy in three prospective trials: UAMS, HOVON65/GMMG-HD4 and MRC Myeloma IX with Affymetrix U133 plus 2.0 microarray data available from diagnostic myeloma PC samples. The BAGS subtypes were significantly associated with progression free (PFS) and overall survival (OS) (PFS, P=3.05e06 and OS, P=1.06e11) in a meta-analysis of 926 pts. The major impact was observed within the PreBII and M subtypes conferred with significant inferior prognosis compared to the Im, N and PC subtypes. Cox proportional hazard meta-analysis documented that the BAGS subtypes added significant and independent prognostic information to the TC classification system and ISS staging. BAGS subtype analysis identified transcriptome differences and a number of novel differentially spliced genes. We have identified hierarchal subtype differences in the myeloma plasma cells, with prognostic impact. This observation support an acquired reversible B-cell trait and phenotypic plasticity as a hallmark, also in MM.
Publication Title
A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [CDF: huex10st_Hs_ENSG_20.0 (huex10st)
Description
Todays diagnostic tests for multiple myeloma (MM) reflect the criteria of the updated WHO classification based on biomarkers and clinicopathologic heterogeneity. To that end, we propose a new subtyping of myeloma plasma cells (PC) by B-cell subset associated gene signatures (BAGS), from the normal B-cell hierarchy in the bone marrow (BM). To do this, we combined FACS and GEP data from normal BM samples to generate classifiers by BAGS for the PreBI, PreBII, immature (Im), nave (N), memory (M) and PC subsets. The resultant tumor assignments in available clinical datasets exhibited similar BAGS subtype frequencies in four cohorts across 1302 individual cases. The prognostic impact of BAGS was analyzed in patients treated with high dose melphalan as first line therapy in three prospective trials: UAMS, HOVON65/GMMG-HD4 and MRC Myeloma IX with Affymetrix U133 plus 2.0 microarray data available from diagnostic myeloma PC samples. The BAGS subtypes were significantly associated with progression free (PFS) and overall survival (OS) (PFS, P=3.05e06 and OS, P=1.06e11) in a meta-analysis of 926 pts. The major impact was observed within the PreBII and M subtypes conferred with significant inferior prognosis compared to the Im, N and PC subtypes. Cox proportional hazard meta-analysis documented that the BAGS subtypes added significant and independent prognostic information to the TC classification system and ISS staging. BAGS subtype analysis identified transcriptome differences and a number of novel differentially spliced genes. We have identified hierarchal subtype differences in the myeloma plasma cells, with prognostic impact. This observation support an acquired reversible B-cell trait and phenotypic plasticity as a hallmark, also in MM.
Publication Title
A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis.
Sample Metadata Fields
Disease
View Samples- Danio rerio
- 16 Downloadable Samples
- IlluminaHiSeq2500
Description
The RNA-binding protein FUS is implicated in transcription, alternative splicing of neuronal genes and DNA repair. Mutations in FUS have been linked to human neurodegenerative diseases such as ALS (amyotrophic lateral sclerosis). We genetically disrupted fus in zebrafish (Danio rerio) using the CRISPR-Cas9 system. The fus knockout animals are fertile and did not show any distinctive phenotype. Mutation of fus induces mild changes in gene expression on the transcriptome and proteome level in the adult brain. We observed a significant influence of genetic background on gene expression and 3’UTR usage, which could mask the effects of loss of Fus. Unlike published fus morphants, maternal zygotic fus mutants do not show motoneuronal degeneration and exhibit normal locomotor activity. Overall design: We performed paired-end sequencing (100bp reads) of the polyA+ transcriptome from brains of five individuals with Fus-/- genotype and four with Fus wild type genotype. Note on RNA-Seq replicates: after performing first RNA sequencing on four replicates of Fus-/- and WT (labeled with the prefix "Sample_imb_ketting_2014_13_") we received a notice from Illumina stating a problem with the library preparation kit lot that was used to prepare the libraries. Due to that, we performed RNA sequencing a second time, using the same input RNA, except for the Fus knockout replicate #3, because there was not enough input RNA left. Instead, a different Fus knockout replicate (#1) was sequenced. However, we compared the mapped reads from sequencing run 1 and sequencing run 2 using plotCorrelaction from DeepTools, and the samples are highly correlated (at least 0.97 and 0.95, Spearman and Pearson correlation respectively). Therefore, we considered first ("Sample_imb_ketting_2014_13_") and second sequencing runs as technical replicates.
Publication Title
Characterization of genetic loss-of-function of Fus in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The DNA double-strand break response is abnormal in myeloblasts from patients with therapy-related acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Disease stage
View Samples