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Mus musculus
14 Downloadable Samples
Illumina HiSeq 2000
Description
Through the generation of humanized FUS mice expressing full length human FUS, we identify that when expressed at near endogenous murine FUS levels both wild-type or ALS- and frontotemporal dementia (FTD)-causing mutations complement the essential function(s) of murine FUS. Replacement of murine FUS with mutant, but not wild-type, human FUS causes stress-mediated induction of chaperones, decreased expression of ion channels/transporters essential for synaptic function, and reduced synaptic activity, without loss of nuclear FUS or its cytoplasmic aggregation. Most strikingly, accumulation of mutant human FUS is shown to activate an integrated stress response and inhibit local, intra-axonal protein synthesis in hippocampal neurons and sciatic nerves. Collectively, our evidence demonstrates that human ALS/FTD-linked mutations in FUS induce a gain-of-toxicity that includes stress-mediated suppression in intra-axonal translation, synaptic dysfunction, and progressive, age-dependent motor and cognitive disease without cytoplasmic aggregation, altered nuclear localization, or aberrant splicing of FUS-bound pre-mRNAs. Methods: RNA from mouse spinal cords of 18-month-old mFUS-/-/hgFUS (WT, R521C or R521H) and their Non-Tg control littermates was extracted with TRIzol. RNA quality was measured using the Agilent Bioanalyzer system and processed using the Illumina TruSeq Stranded mRNA Sample Preparation Kit according to manufacturer's protocols. mRNA profiles were generated by deep sequencing, with n=3 biological replicates per group. Results: We mapped on average 15 million non-redundant reads per sample. Fastq files were aligned to mouse reference genome (mm9 UCSC Genome Browser) using TopHat workfow and the transcript abundance for each annotated protein-coding gene [as fragments per kilobase of transcript per million mapped reads (FPKM)] was estimated by Cufflinks. 13,468 genes which expressed FPKM>=1 were kept for downstream analyses. RNA profiles from normal (Non-Tg) and humanized hgFUSWT mice were almost undistinguishable. Both humanized mutant FUS lines had highly distinct RNA profiles [determined with unsupervised hierarchical clustering and principal component analysis (PCA)], with 709 down and 348 up-regulated genes relative to age-matched Non-Tg or humanized hgFUSWT littermates (P<0.05). These changes uncovered FUS mutant dependent altered pathways that may contribute to ALS/FTD-linked mutant FUS-mediated toxicity. The validation by RT-QPCR of altered expression of 20 genes is shown in Figure 5. Overall design: RNA expression profile of mouse spinal cords from 18-month-old mFUS-/-/hgFUS (WT, R521C or R521H) and their Non-Tg control littermates was obtained by deep sequencing in n=3 indendepent animals per genotype using Illumina HiSeq 2000 sequencer.
Publication Title
ALS/FTD-Linked Mutation in FUS Suppresses Intra-axonal Protein Synthesis and Drives Disease Without Nuclear Loss-of-Function of FUS.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Loss of Rb family in HSC results in their sustained proliferation, impaired homeostasis and extramedullar mobility.
Publication Title
Rb family proteins enforce the homeostasis of quiescent hematopoietic stem cells by repressing Socs3 expression.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 8 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
The conserved multi-subunit Ccr4-Not complex regulates gene expression in diverse ways. In this work, we characterize the suppression of temperature sensitivity associated with a mutation in the gene encoding the scaffold subunit of the Ccr4-Not complex, NOT1, by the deletion of SPT3.
Publication Title
A SAGA-independent function of SPT3 mediates transcriptional deregulation in a mutant of the Ccr4-not complex in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 91 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Publication Title
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Post mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects
Publication Title
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Post mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects
Publication Title
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Post mortem tissue was dissected from two groups of age and gender matched groups of Parkinson and Control subjects
Publication Title
Transcriptional analysis of multiple brain regions in Parkinson's disease supports the involvement of specific protein processing, energy metabolism, and signaling pathways, and suggests novel disease mechanisms.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples
GSE8488- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Objectives: To identify similarities and differences in gene expression data in the MEK/ERK and PI3K pathways and to determine how histone modification affects these same pathways.
Publication Title
Regulation of gene expression by PI3K in mouse growth plate chondrocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Positive selection occurs in the thymic cortex, but critical maturation events occur later in the medulla. We defined the precise stage at which T cells acquire competence to proliferate and emigrate. Transcriptome analysis of late gene changes suggested roles for NF-B and interferon signaling. Mice lacking the IKK kinase TAK1, showed normal positive selection, but a specific block in functional maturation. NF-B signaling provided protection from TNF, and was required for proliferation and emigration. Alternatively, the interferon signature was independent of NF-B, and IFNR deficient thymocytes showed reduced STAT1 levels and phenotypic abnormality, but were competent to proliferate. Thus, both NF-B and tonic IFN signals are involved in the final maturation of thymocytes into nave T cells.
Publication Title
Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 12 Downloadable Samples
- IlluminaHiSeq2500
Description
The function and retention/reprogramming of epigenetic marks during the germline-to-embryo transition is a key issue in developmental and cellular biology, with relevance to stem cell programming and trans-generational inheritance. In zebrafish, DNAme patterns are programmed in transcriptionally-quiescent early cleavage embryos; paternally-inherited patterns are maintained, whereas maternal patterns are reprogrammed to match the paternal pattern. Here we show that a 'placeholder' nucleosome, containing the histone H2A variant H2A.Z(FV) and H3K4me1, occupies virtually all regions lacking DNAme in both sperm and cleavage embryos – residing at promoters encoding housekeeping and early embryonic transcription factors. Upon genome-wide transcriptional onset, genes with the Placeholder become either active H3K4me3-marked or silent H3K4me3/K27me3-marked (bivalent). Importantly, functional perturbation causing Placeholder loss confers DNAme acquisition, whereas acquisition/expansion of Placeholder confers DNA hypomethylation and improper gene activation. Thus, during transcriptionally quiescent stages (gamete-zygote-cleavage), an H2A.Z(FV)/H3K4me1-containing Placeholder nucleosome deters DNAme, poising parental genes for either gene-specific activation or facultative repression. Overall design: Transcript abundance was analyzed for zebrafish sperm, and cleavage stage embryos that were either wild type or mutant for the anp32e gene.
Publication Title
Placeholder Nucleosomes Underlie Germline-to-Embryo DNA Methylation Reprogramming.
Sample Metadata Fields
No sample metadata fields
View Samples