In a transgenic mouse model of Alzheimer disease (AD), cleavage of the amyloid precursor protein (APP) by the -secretase ADAM10 prevented amyloid plaque formation and alleviated cognitive deficits. Furthermore, there was a positive influence of ADAM10 over-expression on neurotransmitter-specific formation of synapses and on synaptic plasticity.
Differential gene expression in ADAM10 and mutant ADAM10 transgenic mice.
Sex, Age
View SamplesWe use mice containing a gene trap in the first intron of the Rest gene, which effectively eliminates transcription from all coding exons, to prematurely remove REST from neural progenitors. We find catastrophic DNA damage that occurs during S-phase of the cell cycle and concominant with activation of p53 pro-apoptotic sgnalling, with consequences including abnormal chromosome separation, apoptosis, and smaller brains.
The REST remodeling complex protects genomic integrity during embryonic neurogenesis.
Specimen part
View SamplesWe use mice containing a gene trap in the first intron of the Rest gene, which effectively eliminates transcription from all coding exons, to prematurely remove REST from neural progenitors. We find catastrophic DNA damage that occurs during S-phase of the cell cycle, with consequences including abnormal chromosome separation, apoptosis, and smaller brains. Further support for persistent effects is the latent appearance of proneural glioblastomas in adult mice also lacking the tumor suppressor, p53. A Rest deficient mouse line generated previously, using a conventional gene targeting approach, does not exhibit these phenotypes, likely due to a remaining C terminal peptide that still binds chromatin and recruits REST chromatin modifiers.Our results indicate that REST-mediated chromatin remodeling is required for proper S-phase dynamics, prior to its well-established role in relieving repression of neuronal genes at terminal differentiation.
The REST remodeling complex protects genomic integrity during embryonic neurogenesis.
Specimen part
View SamplesThis dataset is part of a study that investigated how the hematopoietic system coordinates the rapid and efficient regeneration of the megakaryocytic lineage during stress scenarios. We found that the phenotypic hematopoietic stem cell (HSC) compartment contains stem-like megakaryocyte-committed progenitors (SL-MkPs), a cell population that shares many features with multipotent HSCs and serves as a lineage-restricted emergency pool for inflammatory insults. This dataset contains single-cell RNA sequencing data of 30 hematopoietic stem and progenitor cells which, in the context of our study, confirmed that MK-specfic transcripts are of highly variable expression in HSCs. The dataset further showed that variations in MK transcript expression in HSCs is not correlated with global transcriptomic rearrangements. Overall design: Murine bone marrow cells were sorted by Lin-cKit+CD150+CD48- (referred to as cd150+ in the following) and Lin-cKit+CD150- (referred to as cd150- in the following). Transcriptomes of 11 cd150- and 9 cd150+ HSCs were determined using QUARTZ, a single-cell RNASeq protocol
Inflammation-Induced Emergency Megakaryopoiesis Driven by Hematopoietic Stem Cell-like Megakaryocyte Progenitors.
No sample metadata fields
View SamplesCHD5 is frequently deleted in neuroblastoma, and appears to be a tumor suppressor gene; however, little is known about the role of CHD5. We found CHD5 mRNA was restricted to brain; by contrast most other remodeling ATPases were broadly expressed. CHD5 protein isolated from mouse brain was associated with HDAC2, p66, MTA3 and RbAp46 in a megadalton complex. CHD5 protein was detected in several rat brain regions and appeared to be enriched in neurons. CHD5 protein was predominantly nuclear in primary rat neurons and brain sections. Microarray analysis revealed genes that were upregulated and downregulated when CHD5 was depleted from primary neurons. CHD5 depletion altered expression of neuronal genes, transcription factors, and brain-specific subunits of the SWI/SNF remodeling enzyme. Aging and Alzheimers gene sets were strongly affected by CHD5 depletion from primary neurons. Chromatin immunoprecipitation revealed CHD5 bound to these genes, suggesting the regulation was direct. Together, these results indicate that CHD5 is found in a NuRD-like multi-protein complex. CHD5 is restricted to the brain, unlike the closely related family members CHD3 and CHD4. CHD5 regulates expression of neuronal genes, cell cycle genes and remodeling genes. CHD5 is linked to regulation of aging and Alzheimers genes.
CHD5, a brain-specific paralog of Mi2 chromatin remodeling enzymes, regulates expression of neuronal genes.
Specimen part
View Samples3 pairs of wt and ClC-6 knockout mice, RNA from p14 hippocampus
Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6.
Sex, Age, Specimen part, Subject, Time
View SamplesOrogastral infection of mice with Yersinia enterocolitical leads to HIF-1 alpha activation.To elucidate whether this HIF-1 alpha activation also results in a HIF-1 dependent gene programming, the transcriptomes from Peyers Patches of uninfected and Yersinia enterocolitica infected mice were analyzed by means of of microarray analyses using Affymetrix GeneChip probe arrays (MG-U74Av2). In total, 288 genes were differentially regulated three day after infection in PP compared with the expression of uninfected control mice. Of these 288 genes, 217 were found to be differentially upregulated and from these, 14 genes ( 6.5% of all upregulated genes) are well described to be regulated via HIF-1. These data indicate that orogatral infection with Y. enterocolitica results in HIF-1 dependent gene programmning
Hypoxia-independent activation of HIF-1 by enterobacteriaceae and their siderophores.
No sample metadata fields
View SamplesWe used microarrays to detail the global programme of gene expression underlying cardiac development by HDAC2 and identified distinct classes of up-regulated and down-regulated genes during this process.
Hdac2 regulates the cardiac hypertrophic response by modulating Gsk3 beta activity.
No sample metadata fields
View SamplesWNT1/beta-catenin signaling plays a crucial role in the generation of mesodiencephalic dopaminergic (mdDA) neurons including the Substantia nigra pars compacta (SNc) subpopulation, whose degeneration is a hallmark of Parkinsons Disease (PD). However, the precise functions of WNT/beta-catenin signaling in this context remain unknown. Using mutant mice, primary ventral midbrain (VM) cells and pluripotent stem cells (mouse embryonic stem cells and induced pluripotent stem cells), we show that Dickkopf 3 (DKK3), a secreted glycoprotein that modulates WNT/beta-catenin signaling, is specifically required for the correct differentiation of a rostrolateral mdDA precursor subset into SNc DA neurons.
Dickkopf 3 Promotes the Differentiation of a Rostrolateral Midbrain Dopaminergic Neuronal Subset In Vivo and from Pluripotent Stem Cells In Vitro in the Mouse.
Specimen part
View SamplesWe compared transcriptomes of two ependymoglial populations isolated from adult zebrafish telencephalon. Overall design: Ependymoglial cells are acutely isolated from the adult zebrafish brains form 3 months old transgenic gfap:GFP animals. GFP is experssed in all ependymoglial cells and two populations are separated using GFP intensity in FACS.
The Aryl Hydrocarbon Receptor Pathway Defines the Time Frame for Restorative Neurogenesis.
Specimen part, Subject
View Samples