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GSE48761
Homo sapiens
52 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The premature aging disorder Werner Syndrome (WS) is characterized by early onset of aging phenotypes resembling natural aging. In most WS patients there are mutations in the DNA helicase WRN, an enzyme important in maintaining genome stability and telomere replication. Interestingly, its clinical manifestations reflect a severe degree of deterioration for connective tissue, whereas the central nervous system is less affected. We suggest that the varied vulnerability to aging is regulated by an unknown mechanism that protects specific lineages of stem cells from premature senescence. To address this problem, we reprogrammed patient skin fibroblasts to induced pluripotent stem cells (iPSC). The expression profile for the differentiated normal and WS fibroblasts and undifferentiated iPSC were compared. A distinct expression profile was found between normal and WS fibroblasts, however, few changes of gene expression were found in iPSC. Our findings suggest an erasure of aging phenotype associated with WS in reprogrammed iPSC.
Publication Title
Telomerase protects werner syndrome lineage-specific stem cells from premature aging.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The objective of this study was to understand the genetic mechanisms of Vitamin-A-Deficiency (VAD)-induced arrest of spermatogonial stem-cell differentiation. Vitamin A and its derivatives (the retinoids) participate in many physiological processes including vision, cellular differentiation and reproduction. VAD affects spermatogenesis, the subject of our present study. Spermatogenesis is a highly regulated process of differentiation and complex morphologic alterations that, in the postnatal testis, leads to the formation of sperm in the seminiferous epithelium. VAD causes early cessation of spermatogenesis, characterized by degeneration of meiotic germ cells, leading to seminiferous tubules containing mostly type A spermatogonia and Sertoli cells. In this study, we investigated the molecular basis of VAD on spermatogenesis in mice. We used adult Balb/C mice fed with a Control or VAD diet for an extended period of time (8-28 weeks) and selected two time points (18 and 25 weeks) for microarray analysis.
Publication Title
Long-term vitamin A deficiency induces alteration of adult mouse spermatogenesis and spermatogonial differentiation: direct effect on spermatogonial gene expression and indirect effects via somatic cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
Understanding the mechanisms by which long-term memories are formed and stored in the brain represents a central aim of neuroscience. Prevailing theory suggests that long-term memory encoding involves early plasticity within hippocampal circuits, while reorganization of the neocortex is thought to occur weeks to months later to subserve remote memory storage. Here we report that long-term memory encoding can elicit early transcriptional, structural and functional remodeling of the neocortex. Parallel studies using genome-wide RNA-sequencing, ultrastructural imaging, and whole-cell recording in wild-type mice suggest that contextual fear conditioning initiates a transcriptional program in the medial prefrontal cortex (mPFC) that is accompanied by rapid expansion of the synaptic active zone and postsynaptic density, enhanced dendritic spine plasticity, and increased synaptic efficacy. To address the real-time contribution of the mPFC to long-term memory encoding, we performed temporally precise optogenetic inhibition of excitatory mPFC neurons during contextual fear conditioning. Using this approach, we found that real-time inhibition of the mPFC inhibited activation of the entorhinal-hippocampal circuit and impaired the formation of long-term associative memory. These findings suggest that encoding of long-term episodic memory is associated with early remodeling of neocortical circuits, identify the prefrontal cortex as a critical regulator of encoding-induced hippocampal activation and long-term memory formation, and have important implications for understanding memory processing in healthy and diseased brain states. Overall design: 4 biological replicates per group were analyzed. The material analyzed was medial prefrontal cortex (mPFC; anterior cingulate cortex subregion) from both brain hemispheres, from which total RNA was extracted.
Publication Title
Early remodeling of the neocortex upon episodic memory encoding.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
This study examined transcripts that are enriched in neonatal mouse cochlear supporting cells at postnatal day 1 and postnatal day 6. Supporting cells were purified by FACS sorting for GFP fluorescence from the cochleas of transgenic mice in which a BAC including the LFng locus drives the expression of GFP. Two replicates of GFP+ supporting cells were compared with all other cochlear cell types that were GFP-. We performed this experiment at two different ages, postnatal day 1 and postnatal day 6. Overall design: mRNA profiles of supporting cells (GFP+) and all other cochlear cell types (GFP-), two replicates each, at P1 and P6 mice were generated by deep sequencing using Illumna TruSeq.
Publication Title
Transcriptomic Analysis of Mouse Cochlear Supporting Cell Maturation Reveals Large-Scale Changes in Notch Responsiveness Prior to the Onset of Hearing.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 34 Downloadable Samples
- Illumina HiSeq 2500
Description
Microglia are the resident myeloid-lineage cells in the central nervous system. Despite myriad observations of microglia associated with various tissue pathologies in degenerative disease, their function in and contributions to the pathophysiological processes remain unclear. It is particularly uncertain whether microglia act harmfully to contribute to worsening of degeneration, act beneficially to combat disease-related dysfunction, or perform functions that result in both outcomes. In this dataset, we report RNA sequencing results from mice that undergo inducible ALS/FTLD-like degeneration and subsequent recovery. The goals were to identify whether microglia show transcriptional signatures commensurate with the disease stage or if they remain constant throughout. Additionally, we sought to understand whether there was a particular transcriptional or functional signature associated with functional recovery in the mice. The latter could lead to an understanding of how microglia may be targeted to combat disease and enhance recovery following or during degeneration. Overall design: mRNA profiles from microglia sorted from whole-spinal cord taken from doxycycline (DOX) inducible NEFH-tTa/tetO-208-hTDP43 (rNLS8, (+/+)) mice. In these mice, removal of doxycycline from the diet (DOX-OFF) induces transgenic expression and degeneration and reintroduction (DOX-ON) suppresses expression and enables recovery. We report profiles from rNLS8 mice that were DOX-OFF for 2 weeks (N=8) or 6 weeks (N=7), or DOX-OFF for 6 weeks followed by DOX-ON for 1 week (N=9). We also report profiles from control samples that include: rNLS8 mice that were DOX-ON for 6 weeks (N = 6) as asymptomatic genetic controls and WT (-/-) littermates that were DOX-OFF for 2 weeks (N=4), 6 weeks (N=1), or DOX-OFF for 6 weeks followed by 1 week DOX-ON (N=3) as asymptomatic doxycycline controls.
Publication Title
Microglia-mediated recovery from ALS-relevant motor neuron degeneration in a mouse model of TDP-43 proteinopathy.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
miR-142 gene is specifically and abundantly expressed in hematopoietic cells. Mice that lack this miRNA gene develop immunodeficiency and display altered hematopoeisis.
Publication Title
Altered lymphopoiesis and immunodeficiency in miR-142 null mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The improvement of Ewing's sarcoma (EWS) therapy is currently linked to find strategies to select patients with poor and good prognosis at diagnosis and to generate modified treatment regimens. In this study, we analyze the molecular factors governing EWS response to chemotherapy in order to identify genetic signatures that may be used for risk-adapted therapy.
Publication Title
Overcoming resistance to conventional drugs in Ewing sarcoma and identification of molecular predictors of outcome.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Primordial germ cells (PGCs), the embryonic precursors of eggs and sperm, are a unique model for identifying and studying regulatory mechanisms in singly migrating cells. From their time of specification to eventual colonization of the gonad, mouse PGCs traverse through and interact with many different cell types, including epithelial cells and mesenchymal tissues. Work in drosophila and zebrafish have identified many genes and signaling pathways involved in PGC migration, but little is known about this process in mammals.
Publication Title
Discrete somatic niches coordinate proliferation and migration of primordial germ cells via Wnt signaling.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 22 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
SV40 large T antigen (TAg) contributes to cell transformation, in part, by targeting two well characterized tumor suppressors, pRb and p53. TAg expression affects the transcriptional circuits controlled by Rb and by p53. We have performed a microarray analysis to examine the global change in gene expression induced by wild-type TAg and TAg-mutants, in an effort to link changes in gene expression to specific transforming functions. For this analysis we have used MEFs expressing TAg or infected by SV40. Our analysis indicates that TAg can induce interferon-stimulated genes in MEFs and that this induction depends upon the LXCXE motif and p53 binding.
Publication Title
Induction of interferon-stimulated genes by Simian virus 40 T antigens.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The molecular mechanisms underlying erythroid-specific gene regulation remain incompletely understood. Closely spaced binding sites for GATA, NF-E2/maf and CACCC interacting transcription factors play functionally important roles in globin and other erythroid-specific gene expression. We and others recently identified the CACCC-binding transcription factor ZBP-89 as a novel GATA-1 and NF-E2/mafK interacting partner. Here, we examined the role of ZBP-89 in human globin gene regulation and erythroid maturation using a primary CD34+ cell ex vivo differentiation system. We show that ZBP-89 protein levels rise dramatically during human erythroid differentiation, and that ZBP-89 occupies key cis-regulatory elements within the globin and other erythroid gene loci. ZBP-89 binding correlates strongly with RNA Pol II occupancy, active histone marks, and high-level gene expression. ZBP-89 physically associates with the histone acetyltransferases (HATs) p300 and Gcn5/Trrap, and occupies common sites with Gcn5 within the human globin loci. Lentiviral shRNA knockdown of ZBP-89 results in reduced Gcn5 occupancy, decreased acetylated histone 3 levels, lower globin and erythroid-specific gene expression, and impaired erythroid maturation. Addition of the HDAC inhibitor valproic acid partially reverses the reduced globin gene expression. These findings reveal an activating role for ZBP-89 in human globin gene regulation and erythroid differentiation.
Publication Title
Role of ZBP-89 in human globin gene regulation and erythroid differentiation.
Sample Metadata Fields
Specimen part
View Samples