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GSE80419
Mus musculus
42 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Diabetic foot ulcers (DFU) are one of the major complications in type II diabetes patients and can result in amputation and morbidity. Although multiple approaches are used clinically to help wound closure, many patients still lack adequate treatment. Here we show that IL-20 subfamily cytokines are upregulated during normal wound healing. While there is a redundant role for each individual cytokine in this subfamily in wound healing, mice deficient in IL-22R, the common receptor chain for IL-20, IL-22, and IL-24, display a significant delay in wound healing. Furthermore, IL-20, IL-22 and IL-24 are all able to promote wound healing in type II diabetic db/db mice. When compared to other growth factors such as VEGF and PDGF that accelerate wound healing in this model, IL-22 uniquely induced genes involved in reepithelialization, tissue remodeling and innate host defense mechanisms from wounded skin. Interestingly, IL-22 treatment showed superior efficacy compared to PDGF or VEGF in an infectious diabetic wound model. Taken together, our data suggest that IL-20 subfamily cytokines, particularly IL-20, IL-22, and IL-24, might provide therapeutic benefit for patients with DFU.
Publication Title
IL-22R Ligands IL-20, IL-22, and IL-24 Promote Wound Healing in Diabetic db/db Mice.
Sample Metadata Fields
Treatment, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We aimed to identify genes that are regulated by FGFR1 in brown adipose tissues of adult male ob/ob mice by injecting 1 mg/kg anti-FGFR1 agonistic antibody.
Publication Title
Amelioration of type 2 diabetes by antibody-mediated activation of fibroblast growth factor receptor 1.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We aimed to identify genes that are regulated at downstream of FGFR1/KLB receptor complex in brown adiposetissues of adult male mice on high fat diet by injecting anti-FGFR1/KLB agonisticantibody or human FGF21.
Publication Title
Sustained Brown Fat Stimulation and Insulin Sensitization by a Humanized Bispecific Antibody Agonist for Fibroblast Growth Factor Receptor 1/βKlotho Complex.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
IlluminaHiSeq2500
Description
Heterogeneous nuclear ribonucleoprotein C1/C2 (hnRNPC1/C2) functions as an RNA splicing regulator through co-transcriptional association with nascent mRNA. HnRNPC1/C2 can also bind to double-stranded DNA as a vitamin D response element-binding protein (VDRE-BP), thereby regulating transcriptional activity of the vitamin D receptor (VDR) bound to 1,25-dihydroxyvitamin D (1,25(OH)2D). In this way hnRNPC1/C2 may act as a coupling factor for 1,25(OH)2D-directed transcription and RNA splicing. Studies using MG63 osteoblastic cells confirmed that 1,25(OH)2D-VDR mediated induction of the gene for the enzyme 24-hydroxylase (CYP24A1), involved CYP24A1-specific chromatin and RNA immunoprecipitation of hnRNPC1/C2. Furthermore, small interfering (siRNA) knockdown of hnRNPC1/C2 in MG63 cells and was associated with dysregulated expression of CYP24A1 and an alternatively spliced form of CYP24A1 (CYP24A1-variant 2). Genome-wide analysis of RNA expression and alternative splicing indicated that dual role of hnRNPC1/C2 in directing 1,25(OH)2D-mediated gene expression is not restricted to the classical VDR-target CYP24A1. Knockdown of hnRNPC1/C2 resulted in 3500 differentially expressed genes (DEG), and treatment with 1,25(OH)2D 324 DEG. A further 87 DEG were only observed in 1,25(OH)2D-treated cells in hnRNPC1/C2 knockdown cells. HnRNPC1/C2 knockdown or 1,25(OH)2D treatment also induced alternative splicing (AS) (5039 and 310 AS events respectively). Combined hnRNPC1/C2 knockdown and 1,25(OH)2D treatment resulted in significant overlap between DEG and AS genes, but this was not observed for 1,25(OH)2D treatment alone. These data indicate that hnRNPC1/C2 can act to couple transcriptional and splicing responses to 1,25(OH)2D by binding to both DNA and RNA. Similar mechanisms may also exist for other members of the hnRNP and steroid receptor family. Overall design: Human MG63 osteosarcoma cells (American Type Culture Collection, CRL-1427) were cultured in Dulbecco’s modified Eagle medium (DMEM, high glucose, Gibco, 11995-065) supplemented with 10% Fetal Bovine Serum (FBS) cultured at 37oC with 5% CO2. Crystalline 1,25-dihydroxyvitamin D3 (1,25(OH)2D3, Enzo Life Sciences, BML-DM200-0050) was reconstituted in ethanol. Ethanol (0.1%) was used as vehicle treatment. RNA-seq analysis was carried out using total RNA extracted from MG63 cells using RNAeasy mini kit (Qiagen, 74104), with on-column DNase treatment to remove contaminating genomic DNA. cDNA libraries were prepared using the Illumina TruSeq RNA Sample Preparation Kit (illumina). High-throughput sequencing was performed using an Illumina HiSeq2500 (paired-end, non-strand-specific 107-bp read length). Knockdown and control samples were sequenced together in two flowcells on four lanes.
Publication Title
Concerted effects of heterogeneous nuclear ribonucleoprotein C1/C2 to control vitamin D-directed gene transcription and RNA splicing in human bone cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Tuberculosis remains a major cause of death from an infectious disease worldwide, yet only 10% of people infected with Mycobacterium tuberculosis develop disease. Defining both necessary and sufficient immunologic determinants of protection remains a great scientific challenge. Analysis of peripheral blood gene expression profiles of active tuberculosis patients has identified correlates of risk for disease or pathogenesis. We sought to identify human potential candidate markers of host defense by studying gene expression profiles of macrophages, cells which, upon infection by M. tuberculosis, can mount an antimicrobial response. Weighted gene co-expression network analysis revealed an association between the cytokine, IL-32, and the vitamin D antimicrobial pathway in a network of IFN- and IL-15 induced defense response genes. IL-32 was sufficient for induction of the vitamin D-dependent antimicrobial peptides, cathelicidin and DEFB4, and generation of antimicrobial activity in vitro, dependent on the presence of adequate 25-hydroxyvitamin D. The IL-15 induced defense response macrophage gene network was integrated with ranked pairwise comparisons of gene expression from five different clinical data sets of latent vs. active tuberculosis or healthy controls, and a co-expression network derived from gene expression in patients with tuberculosis undergoing chemotherapy. Together, these analyses identified eight common genes, including IL-32, as molecular markers of latent tuberculosis and the IL-15 induced gene network. Inferring that maintaining M. tuberculosis in a latent state and preventing transition to active disease represents host resistance, we believe these results identify IL-32 as one functional marker and potential correlate of protection against active tuberculosis.
Publication Title
IL-32 is a molecular marker of a host defense network in human tuberculosis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
It has been recently shown that N-ras plays a preferential role in immune cell development and function; specifically: N-ras, but not H-ras or K-ras, could be activated at and signal from the Golgi membrane of immune cells following a low level TCR stimulus. The goal of our studies was to test the hypothesis that N-ras and H-ras played distinct roles in immune cells at the level of the transcriptome.
Publication Title
In TCR-stimulated T-cells, N-ras regulates specific genes and signal transduction pathways.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Hematopoietic stem and progenitor cells are a rare, self-renewing bone marrow resident population capable of giving rise to all circulating hematopoietic cells. They can be used therapuetically for reconstituting defective or ablated hematopoietic systems following chemotherapy, and for inducing tolerance toward allografts of the same haplotype as the HSC donor. There are several sources for HSCs, such as the adult bone marrow, or umblical cord blood, which is more replete with such HSCs. However, HSCs obtained from such sources may be immunogenic, especially if isolated from adult bone marrow. To overcome this issue, our lab has establsihed human induced pluripotent stem cell-derived HPCs with the hope of creating a nonimmunogenic, readily available and unlimited source of HSCs to use for therapy.
Publication Title
Human iPS cell-derived hematopoietic progenitor cells induce T-cell anergy in in vitro-generated alloreactive CD8(+) T cells.
Sample Metadata Fields
Disease
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The cellular response to DNA damage is mediated through multiple pathways that regulate and coordinate DNA repair, cell cycle arrest and cell death. We show that the DNA damage response (DDR) induced by ionizing radiation (IR) is coordinated in breast cancer cells by selective mRNA translation mediated by high levels of translation initiation factor eIF4G1. Increased expression of eIF4G1, common in breast cancers, was found to selectively increase translation of mRNAs involved in cell survival and the DDR, preventing autophagy and apoptosis (Survivin, HIF1, XIAP), promoting cell cycle arrest (GADD45a, p53, ATRIP, Chk1) and DNA repair (53BP1, BRCA1/2, PARP, Rfc2-5, ATM, MRE-11, others). Reduced expression of eIF4G1, but not its homolog eIF4G2, greatly sensitizes cells to DNA damage by IR, induces cell death by both apoptosis and autophagy, and significantly delays resolution of DNA damage foci with little reduction of overall protein synthesis. While some mRNAs selectively translated by higher levels of eIF4G1 were found to use internal ribosome entry site (IRES)-mediated alternate translation, most do not. The latter group shows significantly reduced dependence on eIF4E for translation, facilitated by an enhanced requirement for eIF4G1. Increased expression of eIF4G1 therefore promotes specialized translation of survival, growth arrest and DDR mRNAs that are important in cell survival and DNA repair following genotoxic DNA damage.
Publication Title
DNA damage and eIF4G1 in breast cancer cells reprogram translation for survival and DNA repair mRNAs.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Translation initiation factors have complex functions in cells which are not yet understood. We show that depletion of initiation factor eIF4GI only modestly reduces overall protein synthesis in cells, but phenocopies nutrient-starvation or inhibition of protein kinase mTOR, a key nutrient sensor. eIF4GI depletion impairs cell proliferation, bioenergetics and mitochondrial activity, thereby promoting autophagy. Translation of mRNAs involved in cell growth, proliferation and bioenergetics were selectively inhibited by reduction of eIF4GI, whereas mRNAs encoding proliferation inhibitors and catabolic pathway factors were increased. Depletion or over-expression of other eIF4G family members did not recapitulate these results. The majority of mRNAs that were translationally impaired with eIF4GI depletion were excluded from polyribosomes due to the presence of multiple upstream open reading frames and low mRNA abundance. These results suggest that the high levels of eIF4GI observed in many breast cancers might act to specifically increase proliferation, prevent autophagy and release tumor cells from control by nutrient sensing.
Publication Title
eIF4GI links nutrient sensing by mTOR to cell proliferation and inhibition of autophagy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We established chromate transformed cell lines by chronic exposure of normal human bronchial epithelial BEAS-2B cells to low doses of hexavalent chromium followed by anchorage-independent growth. The gene expression profiles were analyzed in the established cell lines.
Publication Title
Comparison of gene expression profiles in chromate transformed BEAS-2B cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples