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GSE38196
Caenorhabditis elegans
12 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
ATFS-1 has been shown to regulate transcription of mitochondrial chaperone genes such as mtHsp70/hsp-6 and hsp-60 in response to mitocondrial stress. To identify the entire ATFS-1-mediated response, we compared the transcript profiles from wild-type and atfs-1(tm4525) worms raised in the absence and presence of mitochondrial stress.
Publication Title
Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Immunodeficient mouse models have been valuable for studies of human hematopoiesis, but high-fidelity recapitulation of erythropoiesis in most xenograft recipients remains elusive. Recently developed immunodeficient and Kit mutant mice, however, have provided a suitable background to achieve higher-level human erythropoiesis after long-term hematopoietic engraftment. While there has been some characterization of human erythropoiesis in these models, a comprehensive analysis of various developmental stages has not yet been reported. Here, we have utilized cell surface phenotypes, morphologic analyses, and molecular studies to fully characterize human erythropoiesis from multiple developmental stages in immunodeficient and Kit mutant mouse models following long-term hematopoietic stem and progenitor cell engraftment. We show that human erythropoiesis in such models demonstrates complete maturation and enucleation, as well as developmentally appropriate globin gene expression. These results provide a framework for future studies to utilize this model system for interrogating disorders affecting human erythropoiesis and for developing improved therapeutic approaches. Overall design: (mRNA-seq) RNA-seq of human CD235a+ cells isolated 14-16 weeks post-implantation from mouse bone marrow were performed for three biological replicates each of mice xenograted with adult bone marrow-derived human CD34+ cells and cord blood-derived CD34+ cells.
Publication Title
Developmentally-faithful and effective human erythropoiesis in immunodeficient and Kit mutant mice.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression profiling of normal hematopoietic cell subpopulations
Publication Title
Gene expression signatures in childhood acute leukemias are largely unique and distinct from those of normal tissues and other malignancies.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina mouse-6 v1.1 expression beadchips
Description
Human clinical trials in type 1 diabetes (T1D) patients are underway using mesenchymal stem cells (MSC) without prior validation in a mouse model for the disease. In response to this void, we characterized bone marrow-derived murine MSC for their ability to modulate immune responses in the context of T1D, as represented in non-obese diabetic (NOD) mice. In comparison to NOD-, BALB/c-MSC express higher levels of the negative costimulatory molecule PD-L1 and promote a shift toward Th2-like responses in treated NOD mice. In addition, transfer of MSC from resistant strains (i.e. NOR or BALB/c), but not from NOD mice, conferred disease protection when administered to prediabetic NOD mice. The number of BALB/c-MSC trafficking to the pancreatic lymph nodes of NOD mice was higher than in NOD mice provided autologous NOD-MSC. Administration of BALB/c-MSC resulted in reversal of hyperglycemia in 90% of NOD mice (p=0.002). Transfer of autologous NOD-MSC imparted no such therapeutic benefit, and in fact soft tissue and visceral tumors were uniquely observed in this setting (i.e. no tumors were present with BALB/c- or NOR-MSC transfer). These data provide important preclinical data supporting the basis for further development of allogeneic MSC-based therapies for T1D and potentially, other autoimmune disorders.
Publication Title
Immunomodulatory function of bone marrow-derived mesenchymal stem cells in experimental autoimmune type 1 diabetes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Androgen receptor (AR) is a ligand-dependent transcription factor that plays a key role in the onset and progression of prostate cancer. We investigated AR-induced gene expression in prostate cancer cells LNCaP and abl by transfecting siAR / siControl or treating cells with androgen (DHT) over a time course.
Publication Title
Androgen receptor regulates a distinct transcription program in androgen-independent prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
LRF, which is encoded by the ZBTB7A gene and formerly known as POKEMON (POK erythroid myeloid ontogenic factor), was originally identified as a PLZF (promyelocytic leukemia zinc finger) homologue interacting with BCL6 (B-cell lymphoma 6). LRF is a transcription factor that is broadly expressed in hematopoietic lineage cells, but its expression is particularly high in erythroblasts and germinal center (GC) B-cells. The goal of this study is to assess the effect of LRF loss on the LT-HSC transcriptome. Nine days after injection of adult mice with polyinosinic polycytidylic acid (pIpc) to activate Cre, total RNAs were isolated from double-sorted LT-HSCs from LRF Flox/+ Mx1-Cre+ and LRF Flox/Flox Mx1-Cre+ mice and processed for microarray analysis.
Publication Title
LRF-mediated Dll4 repression in erythroblasts is necessary for hematopoietic stem cell maintenance.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Drosophila melanogaster
- 35 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We measured gene expression across the whole genome in a panel of lines selected for a wing shape trait (angular offset). The lines were created in separate experiments, originating from two widely separated populations, and including multiple replicates of one population, but all were created using the same selection regime and trait. Here we evaluate the data with two objectives: 1) to identify candidate wing shape genes for future testing and validation, and 2) to assess variation among lines in the outcome of identical selection regimes
Publication Title
Microarray analysis of replicate populations selected against a wing-shape correlation in Drosophila melanogaster.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The hormone prolactin is implicated in the pathogenesis of breast cancer, and a subset of prolactin-induced gene expression is mediated by HDAC6 activity.
Publication Title
HDAC6 Deacetylates HMGN2 to Regulate Stat5a Activity and Breast Cancer Growth.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Methods: CaMKIIa-creERT2 (Erdmann et al., 2007) and Dicer1f/f (Harfe et al., 2005) were crossed to produce inducible forebrain-restricted Dicer1 knockout mice (Dicer-ifKO) mice. Hippocampal mRNA profiles of 3-month-old wild-type (WT) and (Dicer-ifKO) mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500. Each sample included total RNA isolated from the hippocampus of 3 mice. In total, 12 mice per genotype were used. The sequence reads that passed quality filters were mapped to reference genome (GRCm38/mm10) using Bowtie 2 (2.0.5) and TopHat (2.0.6). SAM/BAM files were further processed with Samtools (0.1.18). Read count quantitations were obtained using Seqmonk (0.26.0). Normalization of read counts and differential expression analysis between genotypes was carried out using DESeq2 R package from Bioconductor (Release 2.13). qRT–PCR validation was performed using SYBR Green assays. Results: We mapped about 13-14 million sequence reads per sample to the mouse genome (build GRCm38/mm10) and quantified 76,938 annotated transcripts. DESeq2 R package was used to normalize the counts and perform the differential expression. Differential analysis output was filtered by FDR threshold (padj < 0.1). This approach led us to identify 641 gene isoforms, corresponding to 314 genes that were differentially regulated in the mouse hippocampus upon Dicer ablation. Conclusions: We extend here the characterization of inducible forebrain-restricted Dicer1 mutants confirming the initial memory improvement. Moreover, we describe several novel phenotypes associated with early Dicer loss in the mature brain including an exacerbated response to seizures, increased CA1 neuron excitability, a pronounced weight gain and enhanced induction of immediate early genes (IEGs) in relevant neuronal nuclei. To identify candidate genes that could explain these phenotypes, we conducted two complementary genomic screens for the miRNAs primarily affected and their targets. Overall, our results explain both the initial and late consequences of Dicer loss in excitatory neurons and indicate that Dicer and the miRNA system play a critical role regulating neuronal homeostasis and responsiveness. Overall design: Hippocampal mRNA profiles of 3-month-old wild-type (WT) and Dicer-ifKO (3 weeks upon tamoxifen administration) male mice were generated by deep sequencing, in triplicate, using Illumina HiSeq 2500. Each sample included total RNA isolated from the hippocampus of 3 mice. In total, 12 mice per genotype were used.
Publication Title
Blocking miRNA Biogenesis in Adult Forebrain Neurons Enhances Seizure Susceptibility, Fear Memory, and Food Intake by Increasing Neuronal Responsiveness.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 83 Downloadable Samples
- Illumina HiSeq 2500, Illumina HiSeq 2000, Illumina Genome Analyzer IIx
Description
Purpose: The ability to rationally manipulate the transcriptional states of cells would be of great use in medicine and bioengineering. We have developed a novel algorithm, NetSurgeon, which utilizes genome-wide gene regulatory networks to identify interventions that force a cell toward a desired expression state. Results: We used NetSurgeon to select transcription factor deletions aimed at improving ethanol production in S. cerevisiae cultures that are catabolizing xylose. We reasoned that interventions that move the transcriptional states of cells utilizing xylose toward the fermentative state typical of cells that are producing ethanol rapidly (while utilizing glucose) might improve xylose fermentation. Some of the interventions selected by NetSurgeon successfully promoted a fermentative transcriptional state in the absence of glucose, resulting in strains with a 2.7-fold increase in xylose import rates, a 4-fold improvement in xylose integration into central carbon metabolism, or a 1.3-fold increase in ethanol production rate. Conclusions: We conclude by presenting an integrated model of transcriptional regulation and metabolic flux that will enable future metabolic engineering efforts aimed at improving xylose fermentation to prioritize functional regulators of central carbon metabolism. Overall design: Mutant and wildtype S. cerevisiae cells were put into 48 hour aerobic batch fermentations of synthetic complete medium supplmented with 2% glucose and 5% xylose and culture samples were taken at 4 hours and 24 hours for transcriptional profiling performed by RNA-Seq analysis. In addition, wildtype S. cerevisiae cells were grown in various single carbon sources for 12 hours and culture samples were taken for transcriptional profiling performed by RNA-Seq analysis.
Publication Title
Model-based transcriptome engineering promotes a fermentative transcriptional state in yeast.
Sample Metadata Fields
Subject
View Samples