We report the RNA-Seq data of microglia from CK-p25 mice visual cortex Overall design: Summary of mice and treatments included in this series: CK-p25 mice - in which the expression of the Cdk5 activator p25 is driven by the excitatory neuron-specific CaMKIIa promoter in an inducible manner (CaMKIIa promoter- tTA x TetO- p25+GFP) (Cruz et al., 2003). Following withdrawal of doxycycline from the diet, CK-p25 exhibit progressive neuronal and synaptic loss with cognitive impairment, which is severe by 6 weeks of p25 induction (Cruz et al., 2003). Tau P301S mice, which express high levels of humanized mutant microtubule-associated protein tau and have tau aggregates that are associated with frontotemporal dementia as early as 5 months of age (Yoshiyama et al., 2007). 8 months old P301S mice, at which age they have synaptic and neuronal loss and cognitive deficits. CK = wild type control mice; CK-p25 + No Stim = CK-p25 mice that did not under go any stimulation; CK-p25 +GENUS = Ck-p25 mice that was stimulated with 40 Hz visual stimulation WT = wild type control mice; P301S + No Stim = P301S mice that did not under go any stimulation; P301S +GENUS = P301S mice that was stimulated with 40 Hz visual stimulation
Gamma Entrainment Binds Higher-Order Brain Regions and Offers Neuroprotection.
Specimen part, Subject
View SamplesGamma 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.
Gamma frequency entrainment attenuates amyloid load and modifies microglia.
Age, Specimen part, Cell line, Subject
View SamplesConcentration- and time-dependent genomic changes in the mouse urinary bladder following exposure to arsenate in drinking water for up to twelve weeks.
Concentration- and time-dependent genomic changes in the mouse urinary bladder following exposure to arsenate in drinking water for up to 12 weeks.
Sex, Age, Specimen part, Subject
View SamplesIn this study, we analyzed how non-coding double stranded RNA (dsRNAs) act as a damage associated molecular pattern (DAMP) in the skin, and how the human cathelicidin AMP LL-37 might influence growth factor production in response to this DAMP. Overall design: Each sample''s RNA was isolated form a single biological source of P6 NHEKs. In total there are 4 samples (non-replicates); Control (PBS treated), 1.75uM LL-37 treated, 0.1ug/ml Poly(I:C) treated, and co-treated with 1.75uM LL-37 and 0.1ug/ml Poly(I:C).
Non-coding Double-stranded RNA and Antimicrobial Peptide LL-37 Induce Growth Factor Expression from Keratinocytes and Endothelial Cells.
Cell line, Treatment, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Myb permits multilineage airway epithelial cell differentiation.
Sex, Specimen part
View SamplesThe epithelium of the pulmonary airway is specially differentiated to provide defense against environmental insults, but also subject to dysregulated differentiation that results in lung disease. The current paradigm for airway epithelial differentiation is a one-step program whereby a p63+ basal epithelial progenitor cell generates a ciliated or secretory cell lineage, but the cue for this transition and whether there are intermediate steps is poorly defined. Here we identify transcription factor Myb as a key regulator that permits early multilineage differentiation of airway epithelial cells. Myb+ cells were identified as p63 and therefore distinct from basal progenitor cells, but were still negative for markers of differentiation.
Myb permits multilineage airway epithelial cell differentiation.
Sex, Specimen part
View SamplesMacrophages have been implicated in breast cancer progression and metastasis, but relatively little is known about the genes and pathways that are involved. Using a conditional allele of Ets2 in the mouse, we have identified Ets2 as a critical gene in tumor associated macrophages (TAMs) that specifically promotes mammary tumor metastasis. Loss of Ets2 in TAMs decreased the frequency and size of lung metastases without impacting primary tumor burden. Expression profiling of isolated tumor macrophages established that Ets2 deficiency resulted in the de-repression of a defined set of anti-angiogenic genes.
An ets2-driven transcriptional program in tumor-associated macrophages promotes tumor metastasis.
Sex, Specimen part
View SamplesThis project describes the establishment and validation of a murine orthotopic xenograft model using fresh human tumor samples that recapitulates the critical components of human pancreatic adenocarcinoma. The authors discuss the proven and theoretical advantages of the model as well as future translational implications.
Clinical, molecular and genetic validation of a murine orthotopic xenograft model of pancreatic adenocarcinoma using fresh human specimens.
Specimen part, Cell line
View SamplesPofut1 is an essential gene that glycosylates proteins containing EGF-like repeats, including Notch Receptors (NotchRs). Work in mice and in Drosophila has shown that O-fucosylation by Pofut1 is required for NotchR ligands to bind to and activate NotchRs. As such, Pofut1 deletion in skeletal myofibers allows for an analysis of potential functions and molecular changes of Pofut1 in skeletal muscle that derive from its expression in skeletal myofibers. In this study we compared gene expression profiles between quadriceps muscles in mice where Protein O-fucosyltransferase 1 (Pofut1) was deleted specifically in skeletal myofibers via use of a human skeletal alpha actin Cre transgene (Scre) and a loxP flanked Pofut1 gene (SCreFF) and mice which bore the only the Scre transgene but did not have floxed Pofut1 alleles (SCre++).
Deletion of <i>Pofut1</i> in Mouse Skeletal Myofibers Induces Muscle Aging-Related Phenotypes in <i>cis</i> and in <i>trans</i>.
Age, Specimen part
View SamplesThis data set is intended as a public resource documenting the identity of roughly 10,000 genes that are abundantly expressed in the mouse cochlea. The data have many uses, including for making comparisons with proteomics studies, and for comparisons of expression profiles with other mouse strains and with other species. The CBA/CaJ strain was chosen because of its lack of known vulnerabilities to premature cochlear degeneration or to extreme reactions to cochlear stresses. It may therefore be considered a normal mouse. No experimental manipulations were done on the mice of this study. Contamination of the results by genes expressed in the surrounding petrous bone and from those in blood cells was minimized.
Immunocytochemical traits of type IV fibrocytes and their possible relations to cochlear function and pathology.
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