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SRP076556
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- Homo sapiens
- 3 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The objective was to identify the molecular mechanisms responsible for in vitro and in vivo efficacy of an anti-MYCN peptide nucleic acid on a preclinical model of alveolar rhabdomyosarcoma. Cells treated with a anti-MYCN PNA exhibit growth arrest and apoptosis, and in vivo tumor growth is blocked.
Publication Title
Antitumor activity of sustained N-myc reduction in rhabdomyosarcomas and transcriptional block by antigene therapy.
Sample Metadata Fields
No sample metadata fields
View Samples- 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
- 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
- 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- Homo sapiens
- 59 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Autism spectrum disorder (ASD) is an early onset neurodevelopmental disorder, which is characterized by disturbances of brain function and behavioral deficits in core areas of impaired reciprocal socialization, impairment in communication skills, and repetitive or restrictive interests and behaviors. ASD is known to have a significant genetic risk, but the underlying genetic variation can be attributed to hundreds of genes. The molecular and pathophysiologic basis of ASD remains elusive because of its genetic heterogeneity and complexity, its high comorbidity with other diseases, and the paucity of brain tissue for study. The invasive nature of collecting primary neuronal tissue from patients might be circumvented through reprogramming peripheral cells to induced pluripotent stem cells (iPSCs), which are able to generate live neurons carrying the genetic variants of disease. This breakthrough allows us to access the cellular and molecular phenotypes of patients with intrinsic autism, that is patients without known genetic disorders or identifiable syndromes or malformations. To do this, we studied a relatively homogeneous patient population of boys with intrinsic autism by excluding patients with known genetic disease or recognizable phenotypes or syndromes, as well as those with profound mental retardation or primary seizure disorders. We generated iPSCs from patients with intrinsic autism, their unaffected male siblings and age-, and sex-matched unaffected controls. And these stem cells were subsequently differentiated into electrophysiologically active neurons. The expression profile for autistic and their unaffected siblings' iPSC-derived neurons were compared. A distinct expression profile was found between autism and sib control. The significantly differentially expressed genes (> 2-fold, FDR < 0.05) in autistic iPSC-derived neurons were significantly enriched for processes related to synaptic transmission, such as neuroactive ligand-receptor signaling and extracellular matrix interactions (FDR < 0.05), and were significantly enriched for genes previously associated with ASD (p < 0.05). Our findings suggest approaches such as iPSC-derived neurons will be an important method to obtain tissue for study that appropriately recapitulates the complex dynamics of an autistic neural cell.
Publication Title
Idiopathic Autism: Cellular and Molecular Phenotypes in Pluripotent Stem Cell-Derived Neurons.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumor associated fibroblasts are known to play an important role in angiogenesis, however the specific signaling pathways playing an important role in this cross talk remain ill defined. Here, we studied how Ets2 transcrpiton factor signaling in tumor associated fibroblasts effected gene expression in surrounding endothelial cells in the MMTV-PyMT mammary tumor model.
Publication Title
Ets2 in tumor fibroblasts promotes angiogenesis in breast cancer.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Gamma oscillations (20-50Hz) are a common local field potential signature in many brain regions that are generated by a resonant circuit between fast-spiking parvalbumin (PV)-positive interneurons and pyramidal cells. Changes in the magnitude and frequency of gamma have been observed in several neuropsychiatric disorders. However, it is unclear how disruptions in gamma oscillations affect cellular pathologies seen in these disorders. Here, we investigate this using the 5XFAD mouse model of Alzheimer’s disease (AD) and find reduced power and magnitude of behaviorally driven gamma oscillatory activity — even before the onset of plaque formation or measurable cognitive decline. Because of the early onset, we aimed to determine if exogenous manipulations of gamma could influence the progression of disease pathology. We find that driving PV-positive neurons at gamma frequency (40Hz) using channelrhodopsin-2 reduced total levels of amyloid-ß (Aß) 40 and 42 isoforms in the hippocampus of 5XFAD mouse. Driving PV-positive neurons at other frequencies, or driving excitatory neurons, did not reduce Aß levels. Furthermore, driving PV-positive neurons reduced enlarged endosomes in hippocampal neurons and cleavage intermediates of APP in 5XFAD mouse. Gene expression profiling revealed a neuroprotective response with morphological transformation of microglia and markedly increased phagocytosis of Aß by microglia. Inspired by these observations, we designed a non-invasive light-flickering paradigm that drives 40Hz gamma activity in mouse visual cortex. The light-flickering paradigm profoundly reduced Aß40 and Aß42 levels in the visual cortex of pre-symptomatic mice and greatly mitigated plaque load in the visual cortex of aged, symptomatic mice. This reduction was completely blocked by a GABA-A antagonist, providing further support for an essential role of GABAergic signaling in mediating neuroprotective gamma activity. Overall, our findings uncover a dramatic and previously unappreciated function of the brain’s endogenous gamma rhythms in reducing the production and increasing the clearance of Aß peptides, whose accumulation is believed to drive the pathogenesis of AD. Overall design: Two to four weeks following virus injection and implant placement, hippocampal CA1 neurons were optigenetically manipulated. During the experiment, 1mW of optical stimulation was delivered for 1h using a 40Hz stimulation protocol.
Publication Title
Gamma frequency entrainment attenuates amyloid load and modifies microglia.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples