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SRP172787
Mus musculus
93 Downloadable Samples
Illumina HiSeq 2000
Description
Background: Activation of microglia, the resident immune cells of the central nervous system, is a prominent pathological hallmark of Alzheimer's disease (AD). However, the gene expression changes underlying microglia activation in response to tau pathology remain elusive. Furthermore, it is not clear how murine gene expression changes relate to human gene expression networks. Methods: Microglia cells were isolated from rTg4510 tau transgenic mice and gene expression was profiled using RNA sequencing. Four age groups of mice (2-, 4-, 6-, and 8-months) were analyzed to capture longitudinal gene expression changes that correspond to varying levels of pathology, from minimal tau accumulation to massive neuronal loss. Statistical and system biology approaches were used to analyze the genes and pathways that underlie microglia activation. Differentially expressed genes were compared to human brain co-expression networks. Results:Statistical analysis of RNAseq data indicated that more than 4000 genes were differentially expressed in rTg4510 microglia compared to wild type microglia, with the majority of gene expression changes occurring between 2- and 4-months of age. These genes belong to four major clusters based on their temporal expression pattern. Genes involved in innate immunity were continuously up-regulated, whereas genes involved in the glutamatergic synapse were down-regulated. Up-regulated innate inflammatory pathways included NF-?B signaling, cytokine-cytokine receptor interaction, lysosome, oxidative phosphorylation, and phagosome. NF-?B and cytokine signaling were among the earliest pathways activated, likely driven by the RELA, STAT1 and STAT6 transcription factors. The expression of many AD associated genes such as APOE and TREM2 was also altered in rTg4510 microglia cells. Differentially expressed genes in rTg4510 microglia were enriched in human neurodegenerative disease associated pathways, including Alzheimer's, Parkinson's, and Huntington's diseases, and highly overlapped with the microglia and endothelial modules of human brain transcriptional co-expression networks. Conclusion: This study revealed temporal transcriptome alterations in microglia cells in response to pathological tau perturbation and provides insights into the molecular changes underlying microglia activation during tau mediated neurodegeneration. Overall design: Compare the microglial cell gene expression changes in rTg4510 tau transgenic mice and wild type at four age groups (2-, 4-, 6-, and 8-months) The rTg4510 mouse is a tauopathy model providing researchers with temporal control over mutant tau transgene expression. The mice express a repressible form of human tau containing the P301L mutation that has been linked with familial frontotemporal dementia. More information can be found here, https://www.alzforum.org/research-models/rtgtaup301l4510
Publication Title
Genome-wide RNAseq study of the molecular mechanisms underlying microglia activation in response to pathological tau perturbation in the rTg4510 tau transgenic animal model.
Sample Metadata Fields
Sex, Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
A375P melanoma cells were treated with 1uM of the MEK inhibitor PD184352 or 0.4uM of the V600EBRAF inhibitor PLX4720 for 2hr, 6hr and 24hrs.
Publication Title
Identification of direct transcriptional targets of (V600E)BRAF/MEK signalling in melanoma.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
High-throughput sequencing of mRNA from mouse lung infected with 1918 pandemic influenza virus revealed that reactive oxygen species scavenger EUK-207 treatment resulted in decreased expression of inflammatory response genes and increased lung metabolic and repair responses.
Publication Title
Treatment with the reactive oxygen species scavenger EUK-207 reduces lung damage and increases survival during 1918 influenza virus infection in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 49 Downloadable Samples
- Illumina HiSeq 2000
Description
We previoiusly identified WDR11 as a potential tumor suppressor in murine medulloblastoma models. To determine additional genes/pathways affected by WDR11 overexpression.To compare somatic mutations of murine models with human medulloblastoma (MB), we performed whole-exome sequencing of mouse tumors representing three distinct MB subgroups: Wnt, Sonic Hedgehog (Shh) and Group 3 (G3). 64 somatic mutations were identified and validated, including 40 predicted to cause amino acid changes. After filtering and cross-species analysis with 366 human MBs from four independent studies, human orthologs for 16 of the 40 mouse genes were found to harbor non-silent mutations in human MB. Loss-of-function Mll2 mutations detected in one mouse tumor were previously reported in 30 of 366 human MBs. In mice with G3 MB, one mouse that died at least 15 days earlier than the others had four novel candidate genes harboring non-silent somatic mutations, Lrfn2, Smyd1, Ubn2 and Wdr11. To test whether these genes had tumor suppressive activity, we constitutively overexpressed each wild type gene in murine G3 tumorspheres followed by intracranial implantation. Mice harboring mouse G3 MB overexpressing WDR11 showed extended survival compared to the other three genes. Genes in the KEGG WNT signaling pathway, including Ccnd1/2/3, Myc and Tcf7l1, were down-regulated in G3 MB tumorspheres overexpressing WDR11, consistent with reduced tumor progression. In conclusion, we demonstrated that common spontaneous mutations were shared between human and murine models of MB suggesting similar molecular mechanisms of tumorigenesis, and identified WDR11 as a protein with tumor suppressive activity in G3 MB. Overall design: Compare differentially expressed genes in WDR11 overexpression group versus control group.
Publication Title
Exome sequencing analysis of murine medulloblastoma models identifies WDR11 as a potential tumor suppressor in Group 3 tumors.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
We''ve recently shown that we can accelerate disease in a model of SLE (the NZB/W F1 model) using an anti-Ox40 mAb treatment regimen. The disease acceleration is rapid (within 2 weeks) but its unclear, mechanistically, how OX40 functions to promote disease. To that end we want to perform RNASeq on the sorted OX40-expressing CD4 T cells during treatment to understand how they function in response to OX40 signaling in vivo Overall design: RNASeq was performed on FACS sorted CD4 T cells from the spleen and kidney of NZB/W F1 lupus mice following anti-Ox40 agonist mAb treatment and disease acceleration
Publication Title
The Ox40/Ox40 Ligand Pathway Promotes Pathogenic Th Cell Responses, Plasmablast Accumulation, and Lupus Nephritis in NZB/W F1 Mice.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
We''ve recently shown that we can accelerate disease in a model of SLE (the NZB/W F1 model) using an anti-Ox40 mAb treatment regimen. The disease acceleration is rapid (within 2 weeks) but its unclear, mechanistically, how Ox40 promotes disease. To that end we performed RNASeq on in vitro cultured CD4 T cells during Ox40 and TCR stimulation (in a reductionist setting) to understand how Ox40 signaling impacts cellular phenotype and function, including with and without TCR stimulation Overall design: RNASeq was performed on in vitro cultured CD4 T cells from the spleen of NZB/W F1 lupus prone mice, following anti-Ox40 mAb and anti-CD3/CD28 bead stimulation
Publication Title
The Ox40/Ox40 Ligand Pathway Promotes Pathogenic Th Cell Responses, Plasmablast Accumulation, and Lupus Nephritis in NZB/W F1 Mice.
Sample Metadata Fields
Cell line, Subject
View Samples- Escherichia coli
- 6 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
DNA microarrays were conducted on E. coli K12 cells stressed with 10 M in N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). Overall, 260 genes varied in expression, 114 up-regulated and 146 down-regulated by Zn deprivation
Publication Title
Characterization of Zn(II)-responsive ribosomal proteins YkgM and L31 in E. coli.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 31 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In an effort to understand the mechanisms of acquired resistance to BRAF inhibitors, we isolated clones that acquired resistance to the BRAF inhibitor GSK2118436 derived from the A375 BRAF V600E mutant melanoma cell line. This resistance clones acquired mutations in NRAS and MEK1. One clones, 16R6-4, acquired two mutations in NRAS Q61K and A146T. Proliferation and western blot analyses demonstrated that these clones were insensitive to single agent GSK2118436 or GSK1120212 (an allosteric MEK inhibitor) but were sensitive to the combination of GSK2118436 and GSK1120212. To further characterize this combination, global transcriptomic analysis was performed in A375 and 16R6-4 after 24 hour treatment with GSK2118436, GSK1120212 or the combination of GSK2118436 and GSK1120212.
Publication Title
Combinations of BRAF, MEK, and PI3K/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Alternative mRNA splicing is the main reason vast mammalian proteomic complexity can be achieved with a limited number of genes. Splicing is physically and functionally coupled to transcription and the rate of transcript elongation has a profound effect on splicing. As the nascent pre-mRNA emerges from transcribing RNA polymerase II (RNAPII), it is assembled into a messenger ribonucleoprotein (mRNP) particle that represents its functional form, and the composition of which determines the fate of the mature transcript4. However, factors that connect the transcribing polymerase with the mRNP particle and help integrate transcript elongation with mRNA splicing remain obscure. Here, we characterized the interactome of chromatin-associated mRNP particles and thereby identified Deleted in Breast Cancer 1 (DBC1) and a protein we named ZIRD. These proteins are subunits of a novel protein complex, named DBIRD, which binds directly to RNAPII. DBIRD regulates alternative splicing of a large set of exons embedded in A/T-rich DNA, and is present at the affected exons. RNAi-mediated DBIRD depletion results in region-specific decreases in transcript elongation, particularly across areas encompassing affected exons. These data indicate that DBIRD complex acts at the interface between mRNP particles and RNAPII, integrating transcript elongation with regulation of alternative splicing.
Publication Title
DBIRD complex integrates alternative mRNA splicing with RNA polymerase II transcript elongation.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 19 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA was purified from lung tissue and isolated Alveolar type II cells. The "SAMPLE_ID" sample description is a sample identifier internal to Genentech. The ID of this project in Genentech''s ExpressionPlot database is PRJ0007671 Overall design: RNA from lung and Alveolar type II cells of the following mutant mice: (1) SpcCreERT2;RosatdTomato n=5 ; (2) SpcCreERT2;RosatdTomato;Etv5ko/loxp n= 5
Publication Title
Transcription factor Etv5 is essential for the maintenance of alveolar type II cells.
Sample Metadata Fields
Specimen part, Subject
View Samples