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SRP126295
Mus musculus
24 Downloadable Samples
Illumina HiSeq 1000
Description
We introduce an in vivo imaging approach that allows us to temporally and spatially resolve the evolution of iNOS and Arginase-positive phagocyte phenotypes in a murine MS model. We show that the polarization of individual phagocytes is established after CNS entry, is dependent on the CNS compartment and can be adapted as inflammatory lesions move from expansion to resolution. Our study thus provides a first real-time analysis of phagocyte specification in the intact CNS. Overall design: Cells were isolated from the Blood and CNS of Arginase-YFP X iNOS-Tomato-Cre mice at clinical onset of Experimental Autoimmune Encephalomyelitis. CD11b_high, CD45_low microglia cells and CD45_positive, CD115_positive, Ly6c_high monocytes were FACS sorted respectively. Total RNA was extracted from the separated populations.
Publication Title
Mononuclear phagocytes locally specify and adapt their phenotype in a multiple sclerosis model.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
KAP1 regulates gene networks controlling mouse B-lymphoid cell differentiation and function.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Chromatin remodeling is fundamental for B cell differentiation. Here, we explored the role in this process of KAP1, the cofactor of KRAB-ZFP transcriptional repressors. B lymphoid-specific Kap1 knockout mice displayed reduced numbers of mature B cells, lower steady-state levels of antibodies and accelerated rates of decay of neutralizing antibodies following viral immunization. Transcriptome analyses of Kap1-deleted B splenocytes revealed an upregulation of PTEN, the enzymatic counter-actor of PIK3 signaling, and of genes encoding DNA damage response factors, cell-cycle regulators and chemokine receptors. ChIP/seq studies established that KAP1 bound at or close to a number of these genes, and controlled chromatin status at their promoters. Genome-wide, KAP1-binding sites avoided active B cell-specific enhancers and were enriched in repressive histone marks, further supporting a role for this molecule in gene silencing in vivo. Likely responsible for tethering KAP1 to at least some of these targets, a discrete subset of KRAB-ZFPs is enriched in B lymphocytes. This work thus reveals the role of KRAB/KAP1-mediated epigenetic regulation in B cell development and homeostasis.
Publication Title
KAP1 regulates gene networks controlling mouse B-lymphoid cell differentiation and function.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
CF's physiopathology is poorly explained by the mutation alone. The oxydative stress could be a major factor of this illness . Study its impact on transcriptome's CF cell line could be ameliorate our understanding of the evolution of cystic fibrosis.
Publication Title
Oxidative stress modulates the expression of genes involved in cell survival in ΔF508 cystic fibrosis airway epithelial cells.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 71 Downloadable Samples
- Illumina HiSeq 4000
Description
In response to viral pathogens, the host upregulates antiviral genes that suppress translation of viral mRNAs. However, induction of such antiviral responses may not be exclusive to viruses as the pathways lie at the intersection of broad inflammatory networks that can also be induced by bacterial pathogens. Using a model of Gram-negative sepsis, we show that propagation of kidney damage initiated by a bacterial origin ultimately involves antiviral responses that result in host translation shutdown. We determined that activation of the Eif2ak2-Eif2a axis is the key mediator of translation initiation block in late phase sepsis. Reversal of this axis mitigated kidney injury. Furthermore, temporal profiling of the kidney translatome revealed that multiple genes involved in formation of the initiation complex were translationally altered during bacterial sepsis. Collectively, our findings implicate that translation shutdown is indifferent to the specific initiating pathogen and is an important determinant of tissue injury in sepsis. Overall design: Bulk 20 um thickness specimens from cross-sectional human kidney biopsies embedded in OCT underwent RNA sequencing. All subjects had ATN, AIN, or a mix of both conditions.
Publication Title
Bacterial sepsis triggers an antiviral response that causes translation shutdown.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Fibroblasts from patients with Type I bipolar disorder (BPD) and their unaffected siblings were obtained from an Old Order Amish pedigree with a high incidence of BPD and reprogrammed to induced pluripotent stem cells (iPSCs). Established iPSCs were subsequently differentiated into neuroprogenitors (NPs) and then to neurons. Transcriptomic microarray analysis was conducted on RNA samples from iPSCs, NPs and neurons matured in culture for either 2 weeks (termed early neurons, E) or 4 weeks (termed late neurons, L). Global RNA profiling indicated that BPD and control iPSCs differentiated into NPs and neurons at a similar rate, enabling studies of differentially expressed genes in neurons from controls and BPD cases. Significant disease-associated differences in gene expression were observed only in L neurons. Specifically, 328 genes were differentially expressed between BPD and control L neurons including GAD1, glutamate decarboxylase 1 (2.5 fold) and SCN4B, the voltage gated type IV sodium channel beta subunit (-14.6 fold). Quantitative RT-PCR confirmed the up-regulation of GAD1 in BPD compared to control L neurons. Gene Ontology, GeneGo and Ingenuity Pathway Analysis of differentially regulated genes in L neurons suggest that alterations in RNA biosynthesis and metabolism, protein trafficking as well as receptor signaling pathways GSK3 signaling may play an important role in the pathophysiology of BPD.
Publication Title
Transcriptomic Analysis of Induced Pluripotent Stem Cells Derived from Patients with Bipolar Disorder from an Old Order Amish Pedigree.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 3000
Description
Bulk RNA Sequencing of Healthy Bone Marrow Mononuclear Cells Overall design: Using standard operating procedures, mononuclear cells from bone marrow aspirates were isolated using Ficoll density gradient separation and cryopreserved in 90% FBS/ 10% DMSO for storage in liquid nitrogen. RNA was harvested from thawed cell vials of BMMCs using AllPrep kits (QIAGEN). Libraries were prepared using TruSeq Stranded Total RNA Sample Preparation Kit (Illumina) with 1ug of RNA input. Sequencing was performed by paired-end 75 nt on Illumina HiSeq 3000.
Publication Title
Human bone marrow assessment by single-cell RNA sequencing, mass cytometry, and flow cytometry.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
C.pn potentiated hyperlipidemia-induced inflammasome activity in cultured macrophages and in foam cells in atherosclerotic lesions of Ldlr/ mice. We discovered that C.pn-induced extracellular IL-1 triggers a negative feedback loop to inhibit GPR109a and ABCA1 expression and cholesterol efflux leading to accumulation of intracellular cholesterol and foam cell formation. Gpr109a and Abca1 were both upregulated in plaque lesions in Nlrp3/ mice in both hyperlipidemic and C.pn infection models.
Publication Title
Chlamydia pneumoniae Hijacks a Host Autoregulatory IL-1β Loop to Drive Foam Cell Formation and Accelerate Atherosclerosis.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- IlluminaHiSeq1500
Description
Estrogens play an important role in breast cancer (BC) development and progression, where the two isoforms of the estrogen receptor (ERa and ERß) are generally co-expressed and mediate the effects of these hormones in cancer cells. ERß has been suggested to exert an antagonist role toward the oncogenic activities of ERa, and for this reason it is considered an oncosuppressor. As clinical evidence regarding a prognostic role for this receptor subtype in hormone-responsive BC is still limited and conflicting, more knowledge is required on the biological functions of ERß in cancer cells. We described previously the ERß and ERa interactomes of BC cells, identifying specific and distinct patterns of protein interactions for the two receptors. In particular, we identified factors involved in mRNA splicing and maturation as important components of both ERa and ERß pathways. Guided by these findings, we investigated here in depth the differences in the early transcriptional events and RNA splicing patterns induced in ERa vs ERa+ERß cells, by expressing ERß in ERa+ human BC MCF-7 cells. High-throughput mRNA sequencing was then performed in both cell lines after stimulation with 17b-estradiol, and the results obtained were compared. Overall design: We investigated here in depth the differences in the early transcriptional events and RNA splicing patterns induced in ERa vs ERa+ERß cells, by expressing ERß in ERa+ human BC MCF-7 cells. High-throughput mRNA sequencing was then performed in both cell lines after stimulation with 17b-estradiol, and the results obtained were compared.
Publication Title
Estrogen receptor beta impacts hormone-induced alternative mRNA splicing in breast cancer cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Preconditioning with a small dose of endotoxin confers unparalleled protection against otherwise lethal models of sepsis. The mechanisms of preconditioning have been investigated extensively in isolated immune cells such as macrophages. However, the role of tissue in mediating the protective response to preconditioning remains unknown. Using the kidney as a model organ, we identify the essential role of the renal epithelial cell in mediating the full expression of protective preconditioning. The protective phenotype is characterized by the clustering of macrophages around S1 segments of proximal tubules, which forms a functional unit mediating protection. To investigate the molecular pathways, we laser microdissected S1 segments from the following: 1) Non-preconditioned mice subjected to single-dose 5 mg/kg lipopolysaccharide (0111:B4, LPS) intraperitoneally for 24 hours. 2) Preconditioned mice subjected to 0.25 mg/kg LPS followed 24 hour later by 5 mg/kg LPS (LPS/LPS). 3) Control mice (saline vehicle).
Publication Title
Endotoxin Preconditioning Reprograms S1 Tubules and Macrophages to Protect the Kidney.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples