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GSE86210
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Chronic lymphocytic leukemia (CLL) is a disorder of mature B cells. Most patients are characterized by indolent disease and an anergic phenotype of their leukemia cells which refers to a state of unresponsiveness to B cell receptor stimulation. Using the E-TCL1 mouse model, we show that B cell-specific ablation of NFAT2 leads to the loss of the anergic phenotype culminating in a significantly compromised life expectancy and histological transformation to aggressive disease. We further define a gene expression signature of anergic CLL cells consisting of several NFAT2-dependant genes employing microarray technology.
Publication Title
NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer. Treatment options are limited and the mechanisms underlying its aggressiveness are poorly understood. Intermittent hypoxia (IH) causes oxidative stress and is emerging as important regulator of tumor metastasis. Vessels in IBC tumors were shown to be immature, which is a primary cause of IH. We therefore investigated the relevance of IH for the modulation of gene expression in IBC cells in order to assess IH as potential regulator of IBC aggressiveness. Gene array analysis of IBC cells following chronic IH (45-60 days) demonstrated increased expression of pro-metastatic genes of the extracellular matrix, such as tenascin-C (TNC; an essential factor of the metastatic niche) and matrix metalloproteinase 9 (MMP9), and of pro-inflammatory processes, such as cyclooxygenase-2 (COX-2). Investigating the oxidative stress-dependent regulation of TNC, we found a gradual sensitivity on mRNA and protein levels. Oxidative stress activated NF-E2-related factor 2 (Nrf2), c-Jun N-terminal kinase (JNK), c-Jun and nuclear factor B (NF-B), but TNC upregulation was only dependent on NF-B activation. Pharmacological inhibition of inhibitor of NF-B (IB) phosphorylation as well as overexpression of IB prevented TNC, MMP9 and COX-2 induction, whereas the pro-inflammatory cytokine interleukin-1 (IL-1) increased their expression levels. Analysis of the gene array data showed NF-B binding sites for 64% of all upregulated genes, linking NF-B and IH-dependent regulation of pro-metastatic gene expression in IBC cells. Our results provide a first link between intermittent hypoxia and pro-metastatic gene expression in IBC cells, revealing a putative novel mechanism for the high metastatic potential of IBC.
Publication Title
Intermittent hypoxia confers pro-metastatic gene expression selectively through NF-κB in inflammatory breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
Description
The development of the central nervous system (CNS) depends on the orchestrated generation of neurons and glia from neural stem cells (NSCs). Although NSCs generate both cell types, they are produced sequentially as neurons are born first and glia later. In humans, this timing is extremely protracted and the underlying mechanisms remain unknown. Deriving glial cells such as astrocytes from human pluripotent stem cells requires 3-6 months of differentiation, greatly impeding their use in human disease modeling and regenerative medicine. Here, we report that expression of the transcription factor nuclear factor IA (NFIA) is sufficient to trigger glial competency in highly neurogenic NSCs and enables the derivation of human astrocytes within 10-12 days. NFIA-induced astrocytes are functional and shown to promote synaptogenesis, protect neurons and generate calcium transients. The mechanism of NFIA-induced glial competency involves rapid but reversible chromatin remodeling, demethylation of the GFAP promoter and a striking effect on the cell cycle. NFIA titration and pharmacological studies indicate that acquisition of a glial-compatible G1 length is critical for achieving glial competency. Our results offer mechanistic insights into human glial competency and enable the routine use of astrocytes for studying human development and disease. Overall design: The timecourse consists of 4 timpoints. Day 0 (d0) represents neurogenic LTNSCs, day 3 (d3) represents overexpression of NFIA with doxycycline and cells were harvested in bulk, day 6 (d6) represents cells sorted for CD44 while NFIA is overexpressed, day 9 (d9) represents CD44+ sorted cells replated in culture without the addition of doxycyline to downregulate NFIA and day 12 (d12) represents the same cultures in d9, but with 3 additional days of no doxycycline treatment. Each timepoint has a minimum of 3 biological replicates. Rosette cells (H9 d0) and neurons (Dapt) were profiled as controls where rosettes were one sample and neurons were performed in duplicate.
Publication Title
NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Hematopoietic stem cells (HSCs) inhabit distinct microenvironments within the adult bone marrow (BM) that govern the delicate balance between HSC quiescence, self-renewal, and differentiation. It has been suggested that quiescent HSCs localize adjacent to BM arteriole endothelial cells in a significant and non-random distribution. This data suggests that the arteriole BM vascular niche may be the primary HSC niche. Because the BM arteriole niche is composed of tightly-associated pericytes, including smooth muscle actin+, LepR+, Nestin+, NG2+, and nonmyelinating Schwann cells, we sought to begin to uncouple the arteriole BM EC niche by examining its capacity to support the maintenance and expansion of HSCs ex vivo and in vivo. We developed a method to isolate and culture BM arteriole endothelial cells in serum-/growth factor-free conditions, allowing for a non-biased approach to examining their instructive function. Utilizing our protocol, we demonstrate that BM endothelial cells, but not BM stromal cells, have the capacity to expand long-term repopulating, multi-lineage HSCs in lieu of complex serum and cytokine supplementation. In addition, transplantation of arteriole endothelial cells promoted rapid hematopoietic recovery and protected HSCs following an LD50 dose of myeloablative irradiation. These data demonstrate that arteriole-derived BM endothelial cells are endowed with the necessary signals to support the self-renewal and regenerative capacity of LT-HSCs and that transplantation of arteriole BM endothelial cells could be used as a therapeutic means to decrease pancytopenias associated with myeloablative treatments to treat a wide array of disease states. Overall design: Transcriptome sequencing of bone marrow endothelial cells and bone marrow stroma, in vitro and in vivo, with and without HSC co-culture.
Publication Title
Vascular Platform to Define Hematopoietic Stem Cell Factors and Enhance Regenerative Hematopoiesis.
Sample Metadata Fields
Specimen part, Disease, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Microgravity as well as chronic muscle disuse are two causes of low back pain originated at least in part from paraspinal muscle deconditioning. At present no study investigated the complexity of the molecular changes in human or mouse paraspinal muscles exposed to microgravity. The aim of this study was to evaluate longissimus dorsi and tongue (as a new potential in-flight negative control) adaptation to microgravity at global gene expression level. C57BL/N6 male mice were flown aboard the BION-M1 biosatellite for 30 days (BF) or housed in a replicate flight habitat on ground (BG). . Global gene expression analysis identified 89 transcripts differentially regulated in longissimus dorsi of BF vs. BG mice (False Discovery Rrate < 0,05 and fold change < -2 and > +2), while only a small number of genes were found differentially regulated in tongue muscle ( BF vs. BG = 27 genes).
Publication Title
Microgravity-Induced Transcriptome Adaptation in Mouse Paraspinal <i>longissimus dorsi</i> Muscle Highlights Insulin Resistance-Linked Genes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Microgravity exposure as well as chronic muscle disuse are two of the main causes of physiological adaptive skeletal muscle atrophy in humans and murine animals in physiological condition. The aim of this study was to investigate, at both morphological and global gene expression level, skeletal muscle adaptation to microgravity in mouse soleus and extensor digitorum longus (EDL). Adult male mice C57BL/N6 were flown aboard the BION-M1 biosatellite for 30 days on orbit (BF) or housed in a replicate flight habitat on Earth (BG) as reference flight control.
Publication Title
Gene Expression Profiling in Slow-Type Calf Soleus Muscle of 30 Days Space-Flown Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 126 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
We hypothesize that germline variation influences susceptibility to aggressive prostate tumor
Publication Title
A systems genetics approach identifies CXCL14, ITGAX, and LPCAT2 as novel aggressive prostate cancer susceptibility genes.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
One clear hallmark of mammalian promoters is the presence of CpG islands (CGIs) at more than two thirds of genes whereas TATA boxes are only present at a minority of promoters. Using genome-wide approaches, we show that GC content and CGIs are major promoter elements in mammalian cells, able to govern open chromatin conformation and support paused transcription. First, we define three classes of promoters with distinct transcriptional directionality and pausing properties which correlate with their GC content. We further analyze the direct influence of GC content on nucleosome positioning and depletion, and show that CGIs correlate with nucleosome depletion both in vivo and in vitro. We also show that transcription is not essential for nucleosome exclusion but influences both a weak +1 and a well-positioned nucleosome at CGI borders. Altogether our data support the idea that CGIs have become an essential feature of promoter structure defining novel regulatory properties in mammals. Overall design: Nucleosome density and positioning were studied by high-throughput sequencing of DNA previously treated with Mnase. In parallel, chIPseq for PolII and H3K27ac were performed in mouse and human with different conditions to assess a potential effect of transcription on nucleosomes properties. To investigate transcription at promoters, we analyzed together with genome-wide Pol II accumulation by ChIP-Seq, paused bidirectional transcripts associated with transcription start sites (TSS RNAs).
Publication Title
CpG islands and GC content dictate nucleosome depletion in a transcription-independent manner at mammalian promoters.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2000
Description
Comparative analysis between oral and cutaneous wound healing in humans using paired and sequential biopsies during the repair process. Overall design: mRNA profiles of Oral/Skin Wound Healing human sample were generated by sequencing using Illumina
Publication Title
Transcriptional signature primes human oral mucosa for rapid wound healing.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples- Homo sapiens
- 259 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
RNA sequencing validation of the Complexity INdex in SARComas prognostic signature.
Sample Metadata Fields
Time
View Samples