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SRP051737
Homo sapiens
7 Downloadable Samples
IlluminaHiSeq2500
Description
During activation, T cells integrate multiple signals from APCs and cytokine milieu. The blockade of these signals can have clinical benefits as exemplified by CTLA4-Ig, which blocks interaction of B7 co-stimulatory molecules on APCs with CD28 on T cells. Variants of CTLA4-Ig, abatacept and belatacept are FDA approved as immunosuppressive agents in arthritis and transplantation whereas murine studies suggested that CTLA4-Ig can be beneficial in a number of other diseases. However, detailed analysis of human CD4 cell hyporesponsivness induced by CTLA4-Ig has not been performed. Herein, we established a model to study effect of CTLA4-Ig on the activation of human naïve T cells in a human mixed lymphocytes system. Comparison of human CD4 cells activated in the presence or absence of CTLA4-Ig, showed that co-stimulation blockade during TCR activation does not affect NFAT signaling but results in decreased activation of NF-kB and AP-1 transcription factors followed by profound decrease in proliferation and cytokine production. The resulting T cells become hyporesponsive to secondary activation and, although capable of receiving TCR signals, fail to proliferate or produce cytokines, demonstrating properties of anergic cells. However, unlike some models of T cell anergy, these cells did not possess increased levels of TCR signaling inhibitor CBLB. Rather, the CTLA4-Ig induced hyporesponsiveness was associated with an elevated level of p27kip1 cyclin-dependent kinase inhibitor. Overall design: Time series. Human resting and activated T cell dUTP mRNA-Seq profiles were generated on Illumina HiSeq2500
Publication Title
Functional characterization of human T cell hyporesponsiveness induced by CTLA4-Ig.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 52 Downloadable Samples
Affymetrix Murine 11K SubA Array (mu11ksuba)
Description
Swiss-Webster B mouse postnatal day 4-5 primary cerebellar culture (pooled from litter mates) treated with sonic hedgehog (Shh), controls (veh), growth arrested (arrest), cycloheximide (cyc) for 1, 3 and 24 hours.
Publication Title
Identification of genes expressed with temporal-spatial restriction to developing cerebellar neuron precursors by a functional genomic approach.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 4000
Description
We used two RNA-Seq methods to measure the the global transcription levels in mouse liver cells. The data here provide insight into the pros and cons of whole transcript method and 3' RNA-Seq method. Overall design: KAPA (whole transcript method) and Lexogen (3' RNA-Seq method) were used to compare global expression in 6 mice of two conditions: 1) 3 normal diet mice 2) 3 iron-loaded diet mice.
Publication Title
A comparison between whole transcript and 3' RNA sequencing methods using Kapa and Lexogen library preparation methods.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Hydrolyzed wheat proteins (HWPs) contained in cosmetics have occasionally caused immediate-type hypersensitivity following repeated skin exposure. Although the Cosmetic Ingredient Review Expert Panel concluded that <3,500 Da HWP is safe for use in cosmetics, it remains biologically unknown how allergenic HWPs evoke immediate-type allergy percutaneously. Keratinocyte-derived thymic stromal lymphopoietin (TSLP) induces type 2 immune responses, which play an essential role in the pathogenesis of immediate-type allergy. Previously, we demonstrated that protein allergens in cultured human keratinocytes strongly induced long-form TSLP (loTSLP) transcription. However loTSLP-regulating signaling by HWP is poorly understood.
Publication Title
An acid-hydrolyzed wheat protein activates the inflammatory and NF-κB pathways leading to long TSLP transcription in human keratinocytes.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The progressive loss of CNS myelin in patients with multiple sclerosis (MS) has been proposed to result from the combined effects of damage to oligodendrocytes and failure of remyelination. A common feature of demyelinated lesions is the presence of oligodendrocyte precursors (OLPs) blocked at a premyelinating stage. However, the mechanistic basis for inhibition of myelin repair is incompletely understood. To identify novel regulators of OLP differentiation, potentially dysregulated during repair, we performed a genome-wide screen of 1040 transcription factor-encoding genes expressed in remyelinating rodent lesions. We report that 50 transcription factor-encoding genes show dynamic expression during repair and that expression of the Wnt pathway mediator Tcf4 (aka Tcf7l2) within OLPs is specific to lesionedbut not normaladult white matter. We report that -catenin signaling is active during oligodendrocyte development and remyelination in vivo. Moreover, we observed similar regulation of Tcf4 in the developing human CNS and lesions of MS. Data mining revealed elevated levels of Wnt pathway mRNA transcripts and proteins within MS lesions, indicating activation of the pathway in this pathological context. We show that dysregulation of Wnt-catenin signaling in OLPs results in profound delay of both developmental myelination and remyelination, based on (1) conditional activation of -catenin in the oligodendrocyte lineage in vivo and (2) findings from APCMin mice, which lack one functional copy of the endogenous Wnt pathway inhibitor APC. Together, our findings indicate that dysregulated Wnt-catenin signaling inhibits myelination/remyelination in the mammalian CNS. Evidence of Wnt pathway activity in human MS lesions suggests that its dysregulation might contribute to inefficient myelin repair in human neurological disorders.
Publication Title
Dysregulation of the Wnt pathway inhibits timely myelination and remyelination in the mammalian CNS.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA-seq was performed using Thy1- and c-Kit+ spermatogonia from 7-days-old PRC1ctrl or dKO mice. Overall design: Duplicate RNA-seq analyses using spermatogonia from 7-days-old PRC1ctrl or dKO mice
Publication Title
Polycomb directs timely activation of germline genes in spermatogenesis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
To determine how aging impacts gene expression in hematopoietic stem cells (HSCs), human CD34+ cells from bone marrow (34BM) and mobilized stem cell products (34P38NPBSC) were examined using microarray-based expression profiling. Differential expression changes were confirmed by microarray comparisons of younger and older expanded T-cell populations.
Publication Title
Decreased IRF8 expression found in aging hematopoietic progenitor/stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Nuclear export of mRNA is an essential process for eukaryotic gene expression. TREX complex couples the gene expression from transcription and splicing to mRNA export. Sub2, a core component of TREX complex in yeast is diversified to two closely related RNA helicases, UAP56 and URH49 in human.UAP56 and URH49 are required for bulk poly (A)+ RNA export but their target genes are quite different. In conclusion, UAP56 and URH49 have a different function in vivo despite the highly similarity.
Publication Title
The closely related RNA helicases, UAP56 and URH49, preferentially form distinct mRNA export machineries and coordinately regulate mitotic progression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
PU.1 is an Ets family transcription factor that is essential for the differentiation of both myeloid and lymphoid cells. PU.1 is down-regulated in classical Hodgkin lymphoma cells via methylation of the PU.1 promoter. To evaluate whether down-regulation of PU.1 is essential for the growth of cHL cells, we generated KM-H2 derived cell lines conditionally express PU.1 by tet-off system (designated KM-H2tetPU.1). Conditonally expressed PU.1 by tetracycline removal induced complete growth arrest and apoptosis in KM-H2 cells. To elucidate the mechanisms underlying cell cycle arrest and apoptosis induced by PU.1, we compared gene expression profiles of KM-H2tetPU.1 cells 0, 1 and 3 days after PU.1 induction, by DNA microarray.
Publication Title
PU.1 is a potent tumor suppressor in classical Hodgkin lymphoma cells.
Sample Metadata Fields
Cell line, Time
View Samples