The mammalian brain is complex, with multiple cell types performing a variety of diverse functions, but exactly how each cell type is affected in aging remains largely unknown. Here we performed a single-cell transcriptomic analysis of young and old mouse brains. We provide comprehensive datasets of aging-related genes, pathways and ligand–receptor interactions in nearly all brain cell types. Our analysis identified gene signatures that vary in a coordinated manner across cell types and gene sets that are regulated in a cell-type specific manner, even at times in opposite directions. These data reveal that aging, rather than inducing a universal program, drives a distinct transcriptional course in each cell population, and they highlight key molecular processes, including ribosome biogenesis, underlying brain aging. Overall, these large-scale datasets provide a resource for the neuroscience community that will facilitate additional discoveries directed towards understanding and modifying the aging process. Overall design: Total of 16 mice brains with raw data for 50,212 single cells and processed data for 37,089 single cells
Single-cell transcriptomic profiling of the aging mouse brain.
Specimen part, Subject
View SamplesWe characterized the gene expression differences in mDA neurons from all PD (Parkinson''s disease) cases (6 independent samples) and controls (8 independent samples), identifying 1,028 differentially expressed genes making up the PD expression signature. Strikingly, MAOB gene was identified as significantly differentially expressed (p = 0.046). The heat map clearly differentiates cases from controls, where interestingly most differentially expressed genes had lower expression in PD cases compared to controls. In the clustering, the RNA expression pattern of the control (C2) with a family history of PD located close to the PD expression signature suggested a susceptibility to PD. Overall design: RNA was isolated from FAC-sorted cells of 14 samples (biological duplicates for each cell line, 7 cell lines in total) using RNeasy Micro Kit (QIAGEN). Quality control of the RNA was carried out with the Agilent Bio-analyzer, Qubit 2.0 at the MPSR of Columbia University. 100 ng of RNA with RIN = 9 were used for generating mRNA-focused libraries using TruSeq RNA Sample Preparation Kit v2 and sequencing on an Illumina 2000/2500 V3 Instrument offered by the Columbia Genome Center.
iPSC-derived dopamine neurons reveal differences between monozygotic twins discordant for Parkinson's disease.
No sample metadata fields
View SamplesHLX was found as a VEGF-A induced gene in HUVEC (B.Schweighofer, submitted). In order to detect genes regulated by HLX HUVEC were infected by recombinant adenovirus expressing HLX for 4, 8, 16 and 32h. RNA was isolated and subjected to microarray analysis using Affymetrix microarray.
The VEGF-regulated transcription factor HLX controls the expression of guidance cues and negatively regulates sprouting of endothelial cells.
No sample metadata fields
View SamplesCD25+ regulatory T cells develop in the thymus (nTregs), but may also be generated in the periphery upon stimulation of naive CD4 T cells under appropriate conditions (iTregs). The mechanisms that regulate the generation of peripheral iTregs are largely unknown.
Analysis of the transcriptional program of developing induced regulatory T cells.
Specimen part, Treatment, Subject, Time
View SamplesIn this experiment, total RNA was extracted from asynchronous population of L1210 cells and hybridized to Affymetrix 430A 2.0 arrays in order to obtain an expression profile of these cells. We have previously mapped the replication timing of the entire mouse genome in this cell line, using mouse CGH arrays (see E-MEXP-1022). We wanted to validate in our system the known correlation between early replication and expression and to analyze its extent. To this end, we have measured the expression in the same cell line (L1210 cells). Two biological replicates were hybridized to 2 identical microarrays. Expression levels were highly similar between the 2 replicates (r=0.98).
Global organization of replication time zones of the mouse genome.
Cell line, Subject
View SamplesCardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective Tissue Growth Factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. To test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase C (PKC) mouse model of DCM. Transgenic mice expressing constitutively active PKC in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to heart failure, cardiac fibrosis, and increased mortality. Beginning at 3 months of age, mice were treated with an antibody to CTGF (FG-3149) or non-immune IgG control antibody for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic function in PKC mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling were elevated in PKC mice, but significantly decreased by CTGF inhibition, however total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKC mice suggests that CTGF inhibition may benefit patients with DCM.
Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy.
Sex, Specimen part, Treatment
View SamplesBasic helix loop helix enhancer 40 (Bhlhe40) is a transcription factor expressed in rodent hippocampus, however, its role in neuronal function is not well understood. Here, we used Bhlhe40 null mice on a congenic C57Bl6/J background (Bhlhe40 KO) to investigate the impact of Bhlhe40 on neuronal excitability and synaptic plasticity. A whole genome expression array predicted that Bhlhe40 KO mice have up-regulated insulin-related pathways and down-regulated neuronal signaling-related pathways in the hippocampus. We validated that insulin degrading enzyme mRNA (Ide) and IDE protein are significantly downregulated in Bhlhe40 KO hippocampi. No significant difference was observed in hippocampal insulin levels. In hippocampal slices, we found CA1 neurons have increased miniature excitatory post-synaptic current (mEPSC) amplitude and decreased inhibitory post-synaptic current (IPSC) amplitude, indicating hyper-excitability in CA1 neurons in Bhlhe40 KO mice. At CA1 synapses, we found a reduction in long term potentiation (LTP) and long term depression (LTD), indicating an impairment in hippocampal synaptic plasticity in Bhlhe40 KO hippocampal slices. Bhlhe40 KO mice displayed no difference in seizure response to the convulsant kainic acid (KA) relative to controls. We found that while Bhlhe40 KO mice have decreased exploratory behavior they do not display alterations in spatial learning and memory. Together this suggests that Bhlhe40 plays a role in modulating neuronal excitability and synaptic plasticity ex vivo, however, Bhlhe40 alone does not play a significant role in seizure susceptibility and learning and memory in vivo. In addition, based on the reduction in IDE protein levels in these mice, there may be dysregulation of other known IDE substrates, namely insulin growth factor (Igf)-1, Igf-2, and Amyloid beta (A).
Mice lacking the transcriptional regulator Bhlhe40 have enhanced neuronal excitability and impaired synaptic plasticity in the hippocampus.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
Specimen part, Treatment
View SamplesWe used microarrays to detail the global gene transcription underlying T cells activation during the first 24 hours after stimulation.
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
Specimen part, Treatment
View SamplesWe used microarrays to detail the global gene transcription effect of Dec1 underlying T cells activation during the first 24 hours after stimulation.
CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
Specimen part, Treatment
View Samples