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GSE78789
Homo sapiens
18 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Recent data suggests that common genetic risk for metabolic disorders such as obesity may be human-specific and exert effects through the central nervous system. To overcome the limitation of human tissue access for study, we have generated induced human pluripotent stem cell (hiPSC)- derived neuronal cultures which recapture many features of hypothalamic neurons within the arcuate nucleus. Here we have comprehensively characterized this model across development and benchmarked these neurons to in vivo events. We also demonstrate their utility in study of obesity risk variants. The dynamic transcriptome across neuronal maturation was examined using microarray and RNAseq methods at 9 time points. K-means clustering of the longitudinal data was conducted to identify co-regulation and miRNA control of biological processes. The transcriptomes were compared to those of 103 samples from 13 brain regions reported in the Genotype-Tissue Expression database (GTEx) using principal components analysis. Genes with proximity to body mass index (BMI)-associated genetic variants were mapped to the developmentally expressed genesets, and enrichment significance was assessed with Fishers exact test. The human neuronal cultures have a transcriptional and physiological profile of NPY/AgRP hypothalamic neurons. The neuronal transcriptomes were highly correlated with adult hypothalamus as compared to any other brain region from the GTEx. Also, roughly 25% of the transcripts showed changes in expression across maturation stages and potential co-regulation of biological processes that mirror neuronal development in vivo. These developmentally expressed genes were significantly enriched for genes in proximity to BMI-associated variants.
Publication Title
Molecular Profiling of Human Induced Pluripotent Stem Cell-Derived Hypothalamic Neurones Provides Developmental Insights into Genetic Loci for Body Weight Regulation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 298 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A comprehensive analysis of adiponectin QTLs using SNP association, SNP cis-effects on peripheral blood gene expression and gene expression correlation identified novel metabolic syndrome (MetS) genes with potential role in carcinogenesis and systemic inflammation.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 202 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Background: Mycobacterium tuberculosis infection is a leading cause of infectious death worldwide. Gene-expression microarray studies profiling the blood transcriptional response of tuberculosis (TB) patients have been undertaken in order to better understand the host immune response as well as to identify potential biomarkers of disease. To date most of these studies have focused on pulmonary TB patients with gene-expression profiles of extra-pulmonary TB patients yet to be compared to those of patients with pulmonary TB or sarcoidosis.
Publication Title
The Transcriptional Signature of Active Tuberculosis Reflects Symptom Status in Extra-Pulmonary and Pulmonary Tuberculosis.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Race
View Samples- Drosophila melanogaster
- 24 Downloadable Samples
Illumina HiSeq 2000
Description
Using RNA-seq, we characterize the global AS regulation of the eight Drosophila SR protein family members Overall design: RNA-seq experiments on two replicate samples from 8 individual SR protein knockdown (exptGroup=S), two replicates of simultaneous SR protein knockdown (XL6:B52 & SC35:B52) (exptGroup=D). Each exptGroup includes duplicate of its own non-specific (NS) controls.
Publication Title
SR proteins control a complex network of RNA-processing events.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 64 Downloadable Samples
- Illumina HiSeq 4000
Description
To identify genes that mediate altered communication between fat body and peripheral tissues, we report the gene expression changes in Drosophila third instar larval fat bodies with or without constitutively-active Toll (Toll10b) to activate innate immune signaling, myristoylated Akt (myrAkt) to activate insulin signaling, or both transgenes to bypass the block from Toll signaling to the upstream part of the insulin signaling pathway Overall design: Comparison of RFP/GFP (Control), Toll10b/GFP (Toll10b), RFP/myrAkt (myrAkt), and Toll10b/myrAkt (Toll10b + myrAkt)
Publication Title
The Toll Signaling Pathway Targets the Insulin-like Peptide Dilp6 to Inhibit Growth in Drosophila.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Escherichia coli
- 18 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
SoxR and SoxS constitute an intracellular signal response system that rapidly detects changes in superoxide levels and modulates gene expression in E. coli.
Publication Title
Rapid changes in gene expression dynamics in response to superoxide reveal SoxRS-dependent and independent transcriptional networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina HiSeq 2000
Description
We profiled total mRNA of pancreas and kidney tissues of 3 different strains (p53-null; In4a/Arf-null and WT) of reprogrammable mouse lines (they all express OCT4, SOX2, KLF4, C-MYC under the control of a tetracycline promoter, activated by doxycycline) Overall design: 5 mice of each genotype were treated with doxycycline to induce the expression of the reprogramming factors, they were sacrificed and total mRNA was extracted from pancreas and kidney tissues (we mapped >24M reads per sample)
Publication Title
Tissue damage and senescence provide critical signals for cellular reprogramming in vivo.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Drosophila melanogaster
- 48 Downloadable Samples
- Affymetrix Drosophila Genome Array (drosgenome1)
Description
Identification of Hox gene downstream genes at embryonic stages 11 and 12<br></br><br></br>Functional diversification of body parts is dependent on the formation of specialized structures along the various body axes. In animals, region-specific morphogenesis along the anterior-posterior axis is controlled by a group of conserved transcription factors encoded by the Hox genes. Although it has long been assumed that Hox proteins carry out their function by regulating distinct sets of downstream genes, only a small number of such genes have been found, with very few having direct roles in controlling cellular behavior. We have quantitatively identified hundreds of Hox downstream genes in Drosophila by microarray analysis, and validated many of them by in situ hybridizations on loss- and gain-of-function mutants. One important finding is that Hox proteins, despite their similar DNA binding properties in vitro, have highly specific effects on the transcriptome in vivo, as expression of many downstream genes responds primarily to a single Hox protein. In addition, a large fraction of downstream genes encodes realizator functions, which directly affect morphogenetic processes, such as orientation and rate of cell divisions, cell-cell adhesion and communication, cell shape and migration, or cell death. Focusing on these realizators, we provide a framework for the morphogenesis of the maxillary segment. Since the genomic organization of Hox genes and the interaction of Hox proteins with specific cofactors are conserved in vertebrates and invertebrates, and similar classes of downstream genes are regulated by Hox proteins across the metazoan phylogeny, our findings represent a first step towards a mechanistic understanding of morphological diversification within a species as well as between species.
Publication Title
Comparative analysis of Hox downstream genes in Drosophila.
Sample Metadata Fields
Age, Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
Estrogen receptor alpha (ESR1) mutations have been identified in hormone therapy resistant breast cancer and primary endometrial cancer. Analyses in breast cancer suggests that mutant ESR1 exhibits estrogen independent activity. In endometrial cancer, ESR1 mutations are associated with worse outcomes and less obesity, however experimental investigation of these mutations has not been performed. Using a unique CRISPR/Cas9 strategy, we introduced the D538G mutation, a common endometrial cancer mutation that alters the ligand binding domain of ESR1, while epitope tagging the endogenous locus. We discovered estrogen-independent mutant ESR1 genomic binding that is significantly altered from wildtype ESR1. The D538G mutation impacted expression, including a large set of non-estrogen regulated genes, and chromatin accessibility, with most affected loci bound by mutant ESR1. Mutant ESR1 is unique from constitutive ESR1 activity as mutant-specific changes are not recapitulated with prolonged estrogen exposure. Overall, D538G mutant ESR1 confers estrogen-independent activity while causing additional regulatory changes in endometrial cancer cells that are distinct from breast cancer cells. Overall design: RNA-seq was used to study the effects of the D538G mutation on gene expression
Publication Title
Estrogen-independent molecular actions of mutant estrogen receptor 1 in endometrial cancer.
Sample Metadata Fields
Cell line, Treatment, Subject, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
We report that whole body PRMT7-/- adult mice display a significant reduction in in muscle mass. RNA sequencing was performed to identify potential PRMT7 targets. We found that top canonical pathways affected by the loss of PRMT7 includes cell cycle and senescence. Overall design: RNA was extracted from tibialis anterior muscles harvested from 3 WT and 3 PRMT7 null mice at 8months. RNA sequencing was performed to compare mRNA in skeletal muscles between WT and KO mice.
Publication Title
PRMT7 Preserves Satellite Cell Regenerative Capacity.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples