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GSE24223
Homo sapiens
179 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we employed transcriptome mRNA profiling of whole blood and purified CD4, CD8 T cells, B cells and monocytes in tandem with high-throughput flow cytometry in 10 kidney transplant patients sampled serially pre-transplant, 1, 2, 4, 8 and 12 weeks. We then mechanistically deconvoluted the early post-transplant immune response. The flow cytometry data confirms depletion of specific cell subsets in response to ATG induction and immunosuppression with sustained decreases in CD4 as well as CD8 cell subsets. A series of T cell activation markers were expressed from Pre-Tx to 12 weeks indicating the evolution of immunity including expansion of CD45RO+CD62L- effector memory cells. Serial whole blood transcript monitoring demonstrated over 2000 differentially expressed genes, with over 80 percent down-regulated Post-Tx. However, cell subset analysis revealed a unique spectrum of subset-specific gene expression with time-dependent changes, with contrasting significant Post-Tx gene upregulation. Our results provide a unique view of the complex evolution of immune/inflammatory molecular networks marking the early post transplant immune response. A critical finding is that analysis of the constituent blood cell subsets provides an entirely new level of detail revealing the nature of this process, effectively deconvoluting the changes that are otherwise lost in the noise of cellular complexity of whole blood.
Publication Title
Deconvoluting post-transplant immunity: cell subset-specific mapping reveals pathways for activation and expansion of memory T, monocytes and B cells.
Sample Metadata Fields
Time
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
To facilitate the search for genetic modifiers that modulate ARPKD disease progression and severity, we sought to generate a congenic rat model that carries the PCK Pkhd1 mutation but is resistant to the development of ARPKD. We transferred the Pkhd1 mutation from the PCK rat onto the genetic background of the FHH (Fawn-Hooded Hypertensive) rat. This newly developed strain, called FHH.Pkhd1, showed significant amelioration of renal disease, and delayed onset of biliary abnormalities. To initiate the exploration for genes and pathways that modulate susceptibility to renal cystogenesis, we investigated transcriptional changes in kidneys from PCK, SD, FHH and FHH.Pkhd1 rats by microarray analysis.
Publication Title
Role of genetic modifiers in an orthologous rat model of ARPKD.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Comparison of mouse ES cells and three different XEN cell cultures.
Publication Title
Imprinted X-inactivation in extra-embryonic endoderm cell lines from mouse blastocysts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
Illumina HiSeq 2000, Affymetrix Human Genome U219 Array (hgu219)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219), Illumina HiSeq 2000
Description
Molecular mechanisms underlying terminal differentiation of B-cells into plasma cells are major determinants of adaptive immunity but remain only partially understood. Here, we present the transcriptional and epigenomic landscapes of cell subsets arising from activation of human naive B-cells and differentiation into plasmablasts. Cell proliferation of activated B cells was linked to a slight decrease in DNA methylation levels but followed by a committal step in which an S-phase-synchronized differentiation switch was associated with an extensive DNA demethylation and local acquisition of 5-hydroxymethylcytosine at enhancers and genes related to plasma cell identity.
Publication Title
Cell-Cycle-Dependent Reconfiguration of the DNA Methylome during Terminal Differentiation of Human B Cells into Plasma Cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 134 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The complex milieu of inflammatory mediators associated with many diseases is often too dilute to directly measure in the periphery, necessitating development of more sensitive measurements suitable for mechanistic studies, earlier diagnosis, guiding selection of therapy, and monitoring interventions. Previously, we determined that plasma of recent-onset (RO) Type 1 diabetes (T1D) patients induce a proinflammatory transcriptional signature in fresh peripheral blood mononuclear cells (PBMC) relative to that of unrelated healthy controls (HC). Here, using an optimized cryopreserved PBMC-based protocol, we compared the signature found between unrelated healthy controls and non-diabetic cystic fibrosis patients possessing Pseudomonas aeruginosa pulmonary tract infection.
Publication Title
Identification of molecular signatures of cystic fibrosis disease status with plasma-based functional genomics.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
HEK293T cells were transfected with the Rbp1-amr or slow (R729H-amr) -amanitin resistant subunit of RNA Pol II and selected with -amanitin 24 hours after transfection for additional 24 hours. Total RNA was extracted and global changes in gene expression were determined using microarray chips.
Publication Title
Disparity between microRNA levels and promoter strength is associated with initiation rate and Pol II pausing.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
FTY720/Fingolimod, an FDA-approved drug for treatment of multiple sclerosis, has beneficial effects in the CNS that are not yet well understood, independent of its effects on immune cell trafficking. Here we show that FTY720 enters the nucleus where it is phosphorylated by sphingosine kinase 2 (SphK2) and nuclear FTY720-P that accumulates there, binds and inhibits class I histone deacetylases (HDACs) enhancing specific histone acetylations. FTY720 is also phosphorylated in mice and accumulates in various brain regions, including hippocampus, inhibits HDACs and enhances histone acetylation and gene expression programs associated with memory and learning leading to improvement of memory impairment independently of its immunosuppressive actions. Our data suggest that sphingosine-1-phosphate and SphK2 play specific roles in memory functions and that FTY720 may be a useful adjuvant therapy to facilitate extinction of aversive memories.
Publication Title
Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Nuclear FTY720-P is a potent inhibitor of class I histone deacetylases (HDACs) that enhances histone acetylations and regulates expression of a restricted set of genes independently of its known effects on canonical signaling through sphingosine-1-phosphate (S1P) receptors. We found that FTY720 is phosphorylated in Era-negative breast cancer cells by nuclear sphingosine kinase 2 and accumulates these cells.
Publication Title
The phosphorylated prodrug FTY720 is a histone deacetylase inhibitor that reactivates ERα expression and enhances hormonal therapy for breast cancer.
Sample Metadata Fields
Cell line
View Samples