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SRP185829
Mus musculus
48 Downloadable Samples
Illumina HiSeq 2500
Description
Graft-versus-host disease (GVHD) is the most serious complication of allogeneic hematopoietic cell transplantation. Notch signals delivered during the first 48 hours after transplantation drive proinflammatory cytokine production in conventional T cells (Tconv) and inhibit expansion of regulatory T cells (Tregs). Short-term Notch inhibition induces long-term GVHD protection. However, it remains unknown whether Notch blockade blunts GVHD through its effects on Tconv, Tregs, or both, and what early Notch-regulated molecular events occur in alloantigen-specific T cells. To address these questions, we engineered T cell grafts to achieve selective Notch blockade in Tconv vs. Tregs and evaluated their capacity to trigger GVHD in mice. Notch blockade in Tconv was essential for GVHD protection, as GVHD severity was similar in recipients of wild-type Tconv combined with Notch-deprived vs. wild-type Tregs. To identify the impact of Notch signaling on the earliest steps of T cell activation in vivo, we established a new acute GVHD model mediated by clonal alloantigen-specific 4C CD4+ Tconv. Notch-deprived 4C T cells had preserved early steps of activation, IL-2 production, proliferation, and T helper polarization. In contrast, Notch inhibition dampened IFN-? and IL-17 production, diminished mTORC1 and ERK1/2 activation, and impaired transcription of a subset of Myc-regulated genes. The distinct Notch-regulated signature had minimal overlap with known Notch targets in T cell leukemia and developing T cells, highlighting the specific impact of Notch signaling in mature T cells. Our findings uncover a unique molecular program associated with pathogenic effects of Notch in T cells at the earliest stages of GVHD. Overall design: 4 samples per cohort (Notch blockade using Dll1/4 neutralizing antibodies vs isotype control antibodies - GD) were analyzed. Additional 4 samples contained 4C T cells retrieved from syngeneic recipients.
Publication Title
Early Notch Signals Induce a Pathogenic Molecular Signature during Priming of Alloantigen-Specific Conventional CD4<sup>+</sup> T Cells in Graft-versus-Host Disease.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
In epidermal differentiation basal keratinocytes detach from the basement membrane, stop proliferating, and express a new set of structural proteins and enzymes, which results in an impermeable protein/lipid barrier that protects us. To define the transcriptional changes essential for this process, we purified large quantities of basal and suprabasal cells from human epidermis, using the expression of b4 integrin as the discriminating factor. The expected expression differences in cytoskeletal, cell cycle and adhesion genes confirmed the effective separation of the cell populations. Using DNA microarray chips, we comprehensively identify the differences in genes expressed in basal and differentiating layers of the epidermis, including the ECM components produced by the basal cells, the proteases in both the basal and suprabasal cells, and the lipid and steroid metabolism enzymes in suprabasal cells responsible for the permeability barrier. We identified the signaling pathways specific for the two populations, and found two previously unknown paracrine and one juxtacrine signaling pathway operating between the basal and suprabasal cells. Furthermore, using specific expression signatures, we identified a new set of late differentiation markers and mapped their chromosomal loci, as well as a new set of melanocyte-specific markers. The data represent a quantum jump in understanding the mechanisms of epidermal differentiation. Basal keratinocytes are defined as integrin b4-positive. Suprabasal sample contains all melanocytes as well.
Publication Title
Transcriptional profiling of epidermal differentiation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
CD8+ tumor infiltrating T cells (TIL) lack effector-phase functions due to defective proximal TCR-mediated signaling shown to result from inactivation of p56lck kinase. We identify a novel interacting partner for p56lck in nonlytic TIL, Protocadherin-18 (pcdh18), and show that pcdh18 is transcribed upon in vitro or in vivo activation of CD8+ central memory T cells (CD44+CD62LhiCD127+) coincident with conversion into effector memory cells (CD44+CD62LloCD127+). Expression of pcdh18 in primary CD8+ effector cells induces the phenotype of nonlytic TIL: defective; proximal TCR signaling, cytokine secretion, and cytolysis; and enhanced AICD. pcdh18 contains a motif (centered at Y505) shared with src kinases (QGQYQP) which is required for the inhibitory phenotype. Thus, pcdh18 is a novel marker of CD8+ effector memory T cells expressed upon cell activation that can function as a negative regulator by restricting the effector phase.
Publication Title
Protocadherin-18 is a novel differentiation marker and an inhibitory signaling receptor for CD8+ effector memory T cells.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Arabidopsis thaliana
- 9 Downloadable Samples
- Arabidopsis Gene 1.0 ST Array (aragene10st)
Description
Land plants can reproduce sexually by developing an embryo from a fertilized egg cell. However, embryos can also be formed from other cell types in many plant species. A key question is thus how embryo identity in plants is controlled, and how this process is modified during non-zygotic embryogenesis. The Arabidopsis zygote divides to produce an embryonic lineage and an extra-embryonic suspensor. Yet, normally quiescent suspensor cells can develop a second embryo when the initial embryo is damaged, or when response to the signaling molecule auxin is locally blocked. Here we have used auxin-dependent suspensor embryogenesis as a model to determine transcriptome changes during embryonic reprogramming. We find that reprogramming is complex and accompanied by large transcriptomic changes prior to anatomic changes. This analysis revealed a strong enrichment for genes encoding components of auxin homeostasis and response among misregulated genes. Strikingly, deregulation among multiple auxin-related gene families converged upon re-establishment of cellular auxin levels or response. This suggests a remarkable degree of feedback regulation to create resilience in auxin response during embryo development. Starting from the transcriptome of auxin-deregulated embryos, we identify an auxin-dependent bHLH transcription factor network that mediates the activity of this hormone in suppressing embryo development from the suspensor.
Publication Title
A Robust Auxin Response Network Controls Embryo and Suspensor Development through a Basic Helix Loop Helix Transcriptional Module.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2500
Description
Reinstatement of DLX3 into SCC13 cells upregulates genes involved with cell cycle exit, signaling, and adhesion whiles downregulates genes involved with cell death, proliferation, and movement. Overall design: We used RNA-sequencing data analysis to assess gene expression in SCC13 cells infected with Adeno-GFP or Adeno-DLX3 in order to understand the effects of DLX3 in a Squamous Cell Carcinoma Cell Line. We identified a specific subset of genes involved in regulation of cell cycle arrest and inhibition of apoptosis.
Publication Title
The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
DLX3 is expressed by differentiated cells in human skin and it has a functional role in epidermal maturation.
Publication Title
The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Impact of brief exercise on circulating monocyte gene and microRNA expression: implications for atherosclerotic vascular disease.
Sample Metadata Fields
Sex, Specimen part, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Impact of brief exercise on peripheral blood NK cell gene and microRNA expression in young adults.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compared PBMC genomic response to exercise in both early (EB) and late-pubertal boys (LB)
Publication Title
Brief bout of exercise alters gene expression in peripheral blood mononuclear cells of early- and late-pubertal males.
Sample Metadata Fields
No sample metadata fields
View Samples