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GSE72267
Homo sapiens
59 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. We study changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls (Discovery set) by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. By applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays, gene expression profiling discriminates patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts were validated by RT-qPCR in an independent cohort of 12 patients and controls (Validation set). Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention.
Publication Title
Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We used wild-type neurons, and directly compared neurons that had been infected with lentiviruses expressing the CaM shRNAs either without or with a wild-type CaM rescue protein. We then analyzed the gene expression patterns in these neurons with the Affymetrix mouse gene ST_1.0 chip. We identified in two independent array studies ~250 genes whose expression was consistently up- or down-regulated by the CaM KD, as compared to the CaM KD/rescue control. As expected, multiple classes of genes were regulated by CaM. Consistent with previous studies, we found that activity-dependent genes, such as Homers, Npas2, Arc and Egr3, were down-regulated by the CaM KD. Interestingly, we observed that several synaptic trafficking proteins were either up- or downregulated by the CaM KD. Among these was a large increase in the expression of Syt2, which can serve as a Ca2+-sensor for synaptic exocytosis; thus, this upregulation of Syt2 by the CaM KD likely accounts for the rescue of the Syt1 KO phenotype. In addition, expression of Syb1 was massively increased, whereas expression of Syt4, Syt9, and syntaxin-1A was decreased. Another intriguing class of proteins whose expression was strongly regulated by CaM were cell-adhesion molecules, such as the synaptic cell-adhesion molecules Lrrtm1, Lrrtm3, and contactin-2. Moreover, we observed up-regulation of sodium channels, and a down-regulation of potassium channels, suggesting that CaM might control the activity-dependent regulation of neuronal excitability. Finally, we detected changes in multiple genes encoding transcription factors, intracellular signal transduction proteins, elements of the cytoskeleton, or metabolic enzymes. It should be noted, however, that despite these multifarious changes, more than 95% of genes showed no CaM KD-induced change, suggesting that the observed CaM KD-dependent expression changes are specific.
Publication Title
Calmodulin suppresses synaptotagmin-2 transcription in cortical neurons.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Recent advances in high density oligonucleotides microarray technology have brought solutions for molecular profiling of human samples at an unprecedented resolution. We mapped whole blood RNA from healthy volunteers and CD34+ from cytapheresis to Human Exon ST 1.0 microarrays. We compared mature blood cells samples with immature CD34+ samples and each of these compartiement with a broad panel of solid tissues. By scanning the expression of over one million known or predicted exons, transcripts such as INPP4B, NEDD9 CD74 and VAV3 were identified as alternatively transcribed between haematopoietic system and solid tissues. The very large combinatorial complexity conveyed by alternative splicing contributes to the specific functional properties of blood cells and haematopoietic stem cells. The gene expression profiles are freely accessible through a dynamic web atlas, providing to the medical and scientific community a simple mean to interrogate and visualize this reference dataset. Finally, the relevance and the precision provided by this exon expression map suggest that exon arrays may be a powerful tool to link specific peripheral whole blood exon signatures modifications to many diseases such as cancer or auto-immune disorders.
Publication Title
Expression map of the human exome in CD34+ cells and blood cells: increased alternative splicing in cell motility and immune response genes.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Objective: Microarray analysis was used to determine the molecular mechanism underlying Fancd2 and Foxo3a double knockout mice HSCs exhaustion.
Publication Title
Fancd2 is required for nuclear retention of Foxo3a in hematopoietic stem cell maintenance.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
Illumina HiSeq 2500
Description
We report the first RNA-Seq experiments profiling of FancC deficiency in B cells. Overall design: RNA-Seq of FancC-dependent gene signatures in mouse mature B cells
Publication Title
Loss of Fancc Impairs Antibody-Secreting Cell Differentiation in Mice through Deregulating the Wnt Signaling Pathway.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Inhibin knockout (Inha-/-) female mice develop sex cord-stromal ovarian cancer with complete penetrance and previous studies demonstrate that the pituitary gonadotropins [follicle stimulating hormone (FSH) and luteinizing hormone (LH)] are influential modifiers of granulosa cell tumor development and progression in inhibin-deficient females. Recent studies have demonstrated that Inha-/- ovarian follicles develop precociously to the early antral stage in prepubertal mice without any increase in serum FSH and these studies suggested that in the absence of inhibins, granulosa cells differentiate abnormally, and thus at sexual maturity may undergo an abnormal response to gonadotropin signaling. To test this hypothesis, we stimulated immature WT and Inha-/- female mice prior to gross tumor formation with gonadotropin analogs, and subsequently examined post-gonadotropin induced ovarian follicle development, as well as preovulatory and hCG-induced gene expression changes in granulosa cells. We find that at three weeks of age, inhibin-deficient ovaries do not show further antral development nor undergo cumulus expansion. Widespread alterations in the transcriptome of gonadotropin-treated Inha-/- granulosa cells suggest that gonadotropins initiate an improper program of cell differentiation in Inha-/- cells. Overall, our experiments reveal that inhibins are essential for the normal gonadotropin-dependent response of granulosa cells.
Publication Title
Defective gonadotropin-dependent ovarian folliculogenesis and granulosa cell gene expression in inhibin-deficient mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Direct conversion of somatic cells into neurons holds great promise for regenerative medicine. However, neuronal conversion is relatively inefficient in human cells compared to mouse cells. It has been unclear what might be the key barriers to reprogramming in human cells. We recently elucidated an RNA program mediated by the polypyrimidine tract binding protein PTB to convert mouse embryonic fibroblasts (MEFs) into functional neurons. In human adult fibroblasts (HAFs), however, we unexpectedly found that invoking the documented PTB–REST–miR-124 loop generates only immature neurons. We now report that the functionality requires sequential inactivation of PTB and the PTB paralog nPTB in HAFs. Inactivation of nPTB triggers another self-enforcing loop essential for neuronal maturation, which comprises nPTB, the transcription factor BRN2, and miR-9. These findings suggest that two separate gatekeepers control neuronal conversion and maturation and consecutively overcoming these gatekeepers enables deterministic reprogramming of HAFs into functional neurons. Overall design: Six RNA-seq libraries are generated by MAPS approach. Total RNA is extracted from induced neuronal cells derived from control shRNA or PTB shRNA treated human adult fibroblasts. Please note that the ''RNA-seq HAF hygro'' sample was on 6 days after switching to N3 media *without* nPTB depletion. The other two ''shPTB 6d'' and ''shPTB 3w'' were on 6 days and 3 weeks respectively after switching to N3 media *with* nPTB depletion.
Publication Title
Sequential regulatory loops as key gatekeepers for neuronal reprogramming in human cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Notch signaling is widely implicated in mouse mammary gland development and tumorigenesis. To investigate the effects of acute activation of Notch signaling in the mammary epithelial compartment, we generated bi-transgenic MMTV-rtTA; TetO-NICD1 (MTB/TICNX) mice that conditionally express a constitutively active NOTCH1 intracellular domain (NICD1) construct in the mammary epithelium upon doxycycline administration.
Publication Title
Notch promotes recurrence of dormant tumor cells following HER2/neu-targeted therapy.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human monocyte derived dendritic cells matured via galectin-1 or LPS.
Publication Title
Galectin-1-matured human monocyte-derived dendritic cells have enhanced migration through extracellular matrix.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mouse oocytes control cumulus cell metabolic processes that are deficient in the oocytes themselves and this delegation is necessary for oocyte development. Oocyte-derived bone morphogenetic factor 15 (BMP15) and growth differentiation factor 9 (GDF9) appear to be key regulators of follicular development. The effect of these factors on cumulus cell function before the preovulatory surge of luteinizing hormone (LH) was assessed by analysis of the transcriptomes of cumulus cells from wildtype (WT), Bmp15-/-, and Bmp15-/- Gdf9+/- double mutant (DM) mice using microarray analysis. The biological themes associated with the most highly-affected transcripts were identified using bioinformatic approaches, IPA and GenMAPP/MAPPFinder. There were 5,332, 7,640, and 2,651 transcripts identified to be significantly changed in the comparisons of Bmp15-/- vs. WT, DM vs. WT, and DM vs. Bmp15-/- respectively by the criteria of FC (fold change) p <0.01. Among theses changed transcripts, 744 were commonly changed in all three pair-wise comparisons, and hence were considered to be the most highly affected transcripts by mutation of Bmp15 and Gdf9. IPA Analyses revealed that metabolism was the major theme associated with the most highly-changed transcripts: glycolysis and sterol biosynthesis were the two most significantly affected pathways. Most of the transcripts encoding enzymes for sterol biosynthesis were down-regulated in both mutant cumulus cells and in WT cumulus cell after oocytectomy. Similarly, there was a reduction of de novo-synthesized cholesterol in these cumulus cells. This suggests that oocytes regulate cumulus cell metabolism, particularly sterol biosynthesis, by promoting the expression of corresponding transcripts. Furthermore, in WT-mice, Mvk, Pmvk, Fdps, Sqle, Cyp51, Sc4mol, and Ebp, which encode enzymes in the sterol biosynthetic pathway, were found to be expressed robustly in cumulus cells, but expression was barely detectable in oocytes. Levels of de novo-synthesized cholesterol were significantly higher in cumulusenclosed oocytes than denuded oocytes. These results indicate that mouse oocytes are deficient in their ability to synthesize cholesterol and require cumulus cells to provide them with products of the sterol biosynthetic pathway. Oocyte-derived BMP15 and GDF9 may promote this metabolic pathway in cumulus cells as compensation for their own deficiencies.
Publication Title
Oocyte regulation of metabolic cooperativity between mouse cumulus cells and oocytes: BMP15 and GDF9 control cholesterol biosynthesis in cumulus cells.
Sample Metadata Fields
No sample metadata fields
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