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SRP114983
Homo sapiens
6 Downloadable Samples
Illumina HiSeq 2000
Description
Dysregulated inflammation is implicated in the pathobiology of aging, yet platelet-leukocyte interactions and downstream inflammatory gene synthesis in older adults remains poorly understood. Highly-purified human platelets and monocytes were isolated from healthy younger (age<45, n=37) and older (age60, n=30) adults and incubated together under autologous and non-autologous conditions. Inflammatory gene synthesis by monocytes, basally and in the presence of platelets, was examined. Next-generation RNA-sequencing allowed for unbiased profiling of the platelet transcriptome in aging. Basal IL-8 and MCP-1 synthesis by monocytes alone did not differ between older and younger adults. However, in the presence of autologous platelets, monocytes from older adults synthesized greater IL-8 (415 vs. 92 ng/mL, p<0.0001) and MCP-1 (867150 vs. 21636 ng/mL, p<0.0001) than younger adults. Non-autologous experiments demonstrated that platelets from older adults were sufficient for upregulating inflammatory gene synthesis by monocytes. Using RNA-seq followed by validation via RT-PCR and immunoblot, we discovered that granzyme A (GrmA), a serine protease not previously identified in human platelets, is increased in aging (~9-fold vs. younger adults, p<0.05) and governs increased IL-8 and MCP-1 synthesis through TLR4 and caspase-1. Inhibiting GrmA reduced the excessive IL-8 and MCP-1 synthesis in older adults to levels similar to younger adults. In summary, human aging is associated with changes in the platelet transcriptome and proteome. GrmA is present and bioactive in human platelets, is higher in older adults, and controls inflammatory gene synthesis by monocytes. Alterations in the platelet molecular signature and downstream signaling to monocytes may contribute to dysregulated inflammatory syndromes and adverse outcomes in older adults.
Publication Title
Granzyme A in Human Platelets Regulates the Synthesis of Proinflammatory Cytokines by Monocytes in Aging.
Sample Metadata Fields
Sex, Age, Specimen part, Disease
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
The immune system relies on the plasticity of its components to produce appropriate responses to frequent environmental challenges. Dendritic cells (DCs) are critical initiators of innate immunity and orchestrate the later and more specific adaptive immunity. The generation of diversity in transcriptional programs is central for effective immune responses. Alternative splicing is widely considered a key generator of transcriptional and proteomic complexity, but its role has been rarely addressed systematically in immune cells. Here we used splicing-sensitive arrays to assess genome-wide gene- and exon-level expression profiles in human DCs in response to a bacterial challenge. We find widespread alternative splicing events and splicing factor transcriptional signatures induced by an E. coli challenge to human DCs. Alternative splicing acts in concert with transcriptional modulation, but these two mechanisms of gene regulation affect primarily distinct functional gene groups. Alternative splicing is likely to have an important role in DC immunobiology because it affects genes known to be involved in DC development, endocytosis, antigen presentation and cell cycle arrest
Publication Title
Genome-wide analysis of alternative splicing during dendritic cell response to a bacterial challenge.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In tumor microenvironment, tumor-associated macrophages (TAMs) have been characterized as M1-like or M2-like phenotype. In this study, we investigated the characteristics and functional roles of different TAMs on cancer metastasis. We isolated TAMs from primary tumor and metastatic lung and performed microarrays to identify the gene expression in distinct TAMs populations.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- IlluminaGenomeAnalyzerIIx
Description
We carried out a genome-wide investigation of the primary transcriptional targets of 1a,25(OH)2D3 in breast epithelial cancer cells using RNA-Seq technology. We identified early transcriptional targets of 1a,25(OH)2D3 involved in adhesion, growth regulation, angiogenesis, actin cytoskeleton regulation, hexose transport, inflammation and immunomodulation, apoptosis, endocytosis and signaling. Furthermore, we found several transcription factors to be regulated by 1a,25(OH)2D3 that subsequently amplify and diversify the transcriptional output driven by 1a,25(OH)2D3 leading finally to a growth arrest of the cells. Moreover, we could show that 1a,25(OH)2D3 elevates the trimethylation of histone H3 lysine 4 at several target gene promoters. Our present transcriptomic analysis of differential expression after 1a,25(OH)2D3 treatment provides a resource of primary 1a,25(OH)2D3 targets that might drive the antiproliferative action in breast cancer epithelial cells.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An integrative genomic approach in oesophageal cells identifies TRB3 as a bile acid responsive gene, downregulated in Barrett's oesophagus, which regulates NF-kappaB activation and cytokine levels.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 32 Downloadable Samples
- NextSeq 500
Description
We report that hippocampal neuronal pentraxin 2 (Nptx2) plays an important role in mediating anxiety. To better understand the mechanism of how Nptx2 alters anxiety, we detected the differential hippocampal gene expression between Nptx2 WT and KO. To do so, we took Nptx2 WT and KO (n = 3) mice for RNA-sequencing (RNAseq)
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- IlluminaHiSeq2000
Description
investigation of lncRNAs deregulated in oncogenic induced senescence.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The involvment of bile acids such as deoxycholic acid (DCA) in gastro-esophageal reflux disease and subsequent Barretts metaplsia has been postulated. This study examines gene expression induced by exposure to DCA in esophageal cells and may be utilised in cross-comparisons with data derived from gene expression studies of Barretts esophagus and associated adenocarcinoma.
Publication Title
An integrative genomic approach in oesophageal cells identifies TRB3 as a bile acid responsive gene, downregulated in Barrett's oesophagus, which regulates NF-kappaB activation and cytokine levels.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The involvment of bile acids such as deoxycholic acid (DCA) in gastro-esophageal reflux disease and subsequent Barretts metaplsia has been postulated. This study examines gene expression induced by exposure to DCA in esophageal cells and may be utilised in cross-comparisions with data derived from gene expression studies of Barretts esophagus and associated adenocarcinoma. Additionally this study may be used to assess divergence in response to bile acids by comparisons with similar study performed in SKGT4 barrett''s assocaited adenocarcinoma cell line.
Publication Title
An integrative genomic approach in oesophageal cells identifies TRB3 as a bile acid responsive gene, downregulated in Barrett's oesophagus, which regulates NF-kappaB activation and cytokine levels.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Mechanosensory hair cells (HCs) are the primary receptors of our senses of hearing and balance. However, very little is known about the transcriptional regulators involved in HC fate determination and differentiation. In this paper, we show that expression of three HC lineage-specific transcription factors: Gfi1, Pou4f3 and Atoh1, can induce a direct commitment towards HC fate during in vitro embryonic stem cell (ESC) differentiation. Induced HCs (iHCs) express numerous HC-specific genes and exhibit polarized membrane protusions reminiscent of stereociliary bundles.
Publication Title
Generation of sensory hair cells by genetic programming with a combination of transcription factors.
Sample Metadata Fields
Specimen part, Cell line
View Samples