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GSE35330
Homo sapiens
23 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Natural killer (NK) cells are lymphocytes that participate in immune responses through their cytotoxic activity and secretion of cytokines and chemokines. They can be activated by interaction with ligands on target cells or by soluble mediators such as cytokines. In addition, soluble HLA-G, a major histocompatibility complex molecule secreted by fetal trophoblast cells during early pregnancy, stimulates resting NK cells to secrete proinflammatory and proangiogenic factors. Human NK cells are abundant in uterus, where they remain after implantation. Soluble HLA-G is endocytosed into early endosomes of NK cells where its receptor, CD158d, initiates a signaling cascade through DNA-PKcs, Akt and NF-kB3. The physiological relevance of this endosomal signaling pathway, and how the fate and function of NK cells during early pregnancy is regulated, is unknown. Here we show that soluble agonists of CD158d trigger DNA damage response signaling and p21 (CIP1/WAF1) expression to promote senescence in primary NK cells. CD158d engagement resulted in morphological alterations in cell size and shape, chromatin remodeling, and survival in the absence of proliferation, all hallmarks of senescence. Microarray analysis revealed a senescence signature of upregulated genes upon sustained activation through CD158d. The proinflammatory and proangiogenic factors secreted by these metabolically active NK cells are part of a senescence associated secretory phenotype (SASP) that promoted tissue remodeling and angiogenesis as assessed by functional readouts of vascular permeability and endothelial cell tube formation. We propose that ligand-induced senescence is a molecular switch for the sustained activation of NK cells in response to soluble HLA-G for the purpose of remodeling the maternal vasculature in early pregnancy.
Publication Title
Cellular senescence induced by CD158d reprograms natural killer cells to promote vascular remodeling.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Toxic shock syndrome (TSS) is an acute, serious systemic illness caused by bacterial superantigens (BSAg). We characterized the early molecular events underlying TSS using our HLA-DR3 transgenic mouse model and studied gene expression profiling using DNA microarrays.
Publication Title
Early gene expression changes induced by the bacterial superantigen staphylococcal enterotoxin B and its modulation by a proteasome inhibitor.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
The liver is one of most important organs in our bodies. It performs many essential functions including metabolism, synthesis, secretion, detoxification, and storage. Hepatocytes are the principal cell type in the liver and are involved in multiple liver-specific functions. There have been several efforts to develop in vitro culture systems capable of maintaining hepatocyte-specific phenotype over long time periods. In hepatic tissue engineering, two commonly used culture systems are the collagen sandwich and monolayers of cells. In this study, genome-wide gene expression profiles of primary hepatocytes were measured over an 8-day period for each cell culture system using Affymetrix GeneChips and analyzed via Gene Set Enrichment Analysis (GSEA), which is a powerful method to elicit biologically meaningful information from microarray data at the level of gene sets. Results indicate that the gene expression in hepatocytes in collagen sandwich cultures gradually diverges from that in monolayer cultures. Gene sets up-regulated in collagen sandwich cultures include those associated with liver metabolic and synthetic functions. These functions are associated with lipid, amino acid, carbohydrate, and alcohol metabolism and bile acid synthesis. Nuclear receptors are up-regulated in collagen sandwiches 24 hours after seeding. Signals transmitted from these receptors may cause the up-regulation of other processes in subsequent days. Cytochrome-P450 monooxygenase expression was initially down-regulated but exhibited up-regulation after 72 hours. Our results provide a baseline for further explorations into the systems biology of engineered liver mimics as well as 2D and 3D co-cultures of primary hepatocytes and non-parenchymal cells.
Publication Title
A comparative study of genome-wide transcriptional profiles of primary hepatocytes in collagen sandwich and monolayer cultures.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 23 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
In this study, genome-wide gene expression profiles of primary hepatocytes and liver sinusoidal endothelial cells (LSECs) were measured at day 12 for each cell culture system using Affymetrix GeneChips and analyzed via Gene Set Enrichment Analysis (GSEA). The culture systems analyzed include the commonly used collagen sandwich and monolayers of hepatocytes, as well as 3-dimensional (3D) engineered liver models that contain hepatocytes and LSECs (3DHL) and hepatocytes, LSECs, and Kupffer cells (3DHLK). Our results highlight the up-regulation of several hepatocyte specific functions in hepatocytes and a novel interplay between Ppara signaling and bile acid biosynthesis in LSECs.
Publication Title
Transcriptomic Analysis of Hepatic Cells in Multicellular Organotypic Liver Models.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 7 Downloadable Samples
Illumina HiSeq 2500
Description
Id proteins have been shown to promote the differentiation of conventional aß and ?dT cells, and to suppress the expansion of invariant Natural Killer T (iNKT) cells and innate-like ?dNKT within their respective cell lineages. However, it remains to be determined whether Id proteins regulate lineage specification in developing T cells that give rise to these distinct cell fates. Here we report that in the absence of Id2 and Id3 proteins, E2A prematurely activates genes critical for the iNKT cell lineage prior to TCR expression. Lack of Id proteins also promotes a biased TCR rearrangement in favor of iNKT cell fate prior to selection at the CD4+CD8+ double positive (DP) stage. Enhanced iNKT development in Id3-deficient mice lacking ?dNKT cells suggests that Id3 regulates the lineage competition between these populations. RNA-Seq analysis establishes E2A as the transcriptional regulator of both iNKT and ?dNKT development. In the absence of pre-TCR signaling, Id2/Id3 deletion gives rise to a large population of iNKT cells and a unique innate-like DP population, despite the block in conventional aß T cell development. The transcriptional profile of these unique DP cells reflects enrichment of innate-like signature genes, including PLZF (Zbtb16) and Granzyme A (Gzma). Results from these genetic models and genome-wide analyses suggest that Id proteins suppress E2A-driven innate-like T cell programs prior to TCR selection to enforce predominance of conventional T cells. Overall design: The RNA-Seq experiment included WT DP, pTaKO DP, L-DKO DP and L-DKO pTaKO (abbreviated as LP) DP cells (where L-DKO refers to mice deficient in both Id2/Id3). Each replicate represents cells from a single mouse. One pTaKO DP (#1) sample was removed from analysis due to low quality of sequencing. All mice were B6/129 hybrids and littermates.
Publication Title
Id Proteins Suppress E2A-Driven Invariant Natural Killer T Cell Development prior to TCR Selection.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Id2 Collaborates with Id3 To Suppress Invariant NKT and Innate-like Tumors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Inhibitor of DNA binding proteins (ID), including Id1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins have been widely reported to be associated with a broad spectrum of tumors, recent studies have identified that Id3 also plays a tumor suppressor role in the development of Burkitts lymphoma in humans and Hepatosplenic T cell lymphomas in mice. However, there is a lack of evidence to suggest the tumor suppressor roles for other Id genes, particularly Id2, which is highly expressed in many T lymphocytes. In this study we report that Id2 plays a tumor suppressive role in collaboration with Id3 in developing T cells in mice. We found that there was rapid lymphoma development in Id2f/fId3f/fLckCre mice caused by unchecked neonatal expansion of invariant Natural Killer T (iNKT) cells and a unique subset of innate-like, CD1d-independent T cells. These tumors also gave rise to lymphomas in Rag-deficient mice, reaffirming the inherent tumorigenic potential of these cells. Microarray analysis revealed a significantly modified program in expanding iNKT cells that ultimately contributed to tumorigenesis. We found chromosome instability and significant upregulation of several different signaling pathways, including pathways for multiple chemokines, cytokines and their receptors, in these tumors. While Id proteins are being considered as potential therapeutic targets in some cancer models, our results highlight the possibility of aggravated tumorigenesis upon suppression of Id2 and Id3.
Publication Title
Id2 Collaborates with Id3 To Suppress Invariant NKT and Innate-like Tumors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 4000
Description
Inhibitor of DNA binding proteins (ID), including Id1-4, are transcriptional regulators involved in promoting cell proliferation and survival in various cell types. Although upregulation of Id proteins have been widely reported to be associated with a broad spectrum of tumors, recent studies have identified that Id3 also plays a tumor suppressor role in the development of Burkitt’s lymphoma in humans and Hepatosplenic T cell lymphomas in mice. However, there is a lack of evidence to suggest the tumor suppressor roles for other Id genes, particularly Id2, which is highly expressed in many T lymphocytes. In this study we report that Id2 plays a tumor suppressive role in collaboration with Id3 in developing T cells in mice. We found that there was rapid lymphoma development in Id2f/fId3f/fLckCre mice caused by unchecked neonatal expansion of invariant Natural Killer T (iNKT) cells and a unique subset of innate-like, CD1d-independent T cells. These tumors also gave rise to lymphomas in Rag-deficient mice, reaffirming the inherent tumorigenic potential of these cells. Microarray analysis revealed a significantly modified program in expanding iNKT cells that ultimately contributed to tumorigenesis. Similar pathways in CD1dTet- tumors were verified by RNASeq. We found chromosome instability and significant upregulation of several different signaling pathways, including pathways for multiple chemokines, cytokines and their receptors, in these tumors. While Id proteins are being considered as potential therapeutic targets in some cancer models, our results highlight the possibility of aggravated tumorigenesis upon suppression of Id2 and Id3. Overall design: Pre-malignant iNKT (TCRß+CD1dTet+) cells were sorted from three 20 day old L-DKO mice. Lymphoma cells (T cells that are CD1dTet+ or CD1dTet-) were sorted from tissues of 18-37 week old L-DKO mice. Total RNA was extracted, and paired-end libraries were prepared and sequenced using Illumina Hi-Seq 4000
Publication Title
Id2 Collaborates with Id3 To Suppress Invariant NKT and Innate-like Tumors.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cardiac malformations due to aberrant development of the atrioventricular (AV) valves are among the most common forms of congenital heart disease. At localized swellings of extracellular matrix known as the endocardial cushions, the endothelial lining of the heart undergoes an epithelial to mesenchymal transition (EMT) to form mesenchymal progenitors of the AV valves. Further growth and differentiation of these mesenchymal precursors results in formation of portions of the atrial and ventricular septae, and generation of thin, pliable valves. The transcription factor Gata4 is expressed in the endothelium and mesenchyme of the AV valves. Using a Tie2-Cre transgene, we selectively inactivated Gata4 within endothelial-derived cells. Mutant endothelium failed to undergo EMT, resulting in hypocellular cushions. Mutant cushions had decreased levels of Erbb3, an EGF-family receptor essential for EMT in the atrioventricular cushions. In Gata4 mutant embryos, Erbb3 downregulation was associated with impaired activation of Erk, which is also required for EMT. Expression of a Gata4 mutant protein defective in interaction with Friend of Gata (FOG) cofactors rescued the EMT defect, but resulted in decreased proliferation of mesenchyme and hypoplastic cushions that failed to septate the ventricular inlet. We demonstrate two novel functions of Gata4 in development of the AV valves. First, Gata4 functions as an upstream regulator of an Erbb3-Erk pathway necessary for EMT, and second, Gata4 acts to promote cushion mesenchyme growth and remodeling.
Publication Title
Development of heart valves requires Gata4 expression in endothelial-derived cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 27 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
ACTL6A Is Co-Amplified with p63 in Squamous Cell Carcinoma to Drive YAP Activation, Regenerative Proliferation, and Poor Prognosis.
Sample Metadata Fields
Cell line, Treatment
View Samples