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SRP075917
Mus musculus
15 Downloadable Samples
Illumina HiSeq 2500, NextSeq 500
Description
Rett syndrome is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MECP2), an epigenetic regulator of mRNA transcription. Here we report a test of the hypothesis of shared pathophysiology of Rett syndrome and fragile X, another monogenic cause of autism and intellectual disability. In fragile X, the loss of the mRNA translational repressor FMRP leads to exaggerated protein synthesis downstream of metabotropic glutamate receptor 5 (mGluR5). We found that mGluR5- and protein synthesis-dependent synaptic plasticity is similarly altered in area CA1 of Mecp2 KO mice. CA1 pyramidal cell-type-specific, genome-wide profiling of ribosome-bound mRNAs was performed in wild-type and Mecp2 KO hippocampal CA1 neurons to reveal the MeCP2-regulated 'translatome'. We found significant overlap between ribosome-bound transcripts overexpressed in the Mecp2 KO and FMRP mRNA targets. These tended to encode long genes that are functionally related to either cytoskeleton organization or the development of neuronal connectivity. In the Fmr1 KO mouse, chronic treatment with mGluR5 negative allosteric modulators (NAMs) has been shown to ameliorate many mutant phenotypes by correcting excessive protein synthesis. In the Mecp2 KO mice we found that mGluR5 NAM treatment significantly reduces the level of overexpressed ribosome-associated transcripts, particularly those that are also FMRP targets. Some Rett phenotypes were also ameliorated by treatment, most notably hippocampal cell size and life span. Together, these results suggest a potential mechanistic link between MeCP2-mediated transcription regulation and mGluR5/FMRP-mediated protein translation regulation through co-regulation of a subset of genes relevant to synaptic functions. Overall design: TRAP-seq analysis of the effect of negative modulator of mGluR5 on the CA1 neurons (marked by Cck-EGFP-L10a) of a mouse model of Rett syndrome
Publication Title
Negative Allosteric Modulation of mGluR5 Partially Corrects Pathophysiology in a Mouse Model of Rett Syndrome.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that macrophages in the spleen are phenotypically distinct in male compared to female mice at 12 hours (h) after infection. This innate immune profile mirrors and predicts the cardiac immune response during acute myocarditis.
Publication Title
The innate immune response to coxsackievirus B3 predicts progression to cardiovascular disease and heart failure in male mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Men are at an increased risk of dying from heart failure caused by inflammatory heart diseases such as atherosclerosis, myocarditis and dilated cardiomyopathy (DCM). We previously showed that immune responses in the heart are phenotypically distinct in male compared to female mice 10 days after infection resulting in severe DCM in males.
Publication Title
Testosterone and interleukin-1β increase cardiac remodeling during coxsackievirus B3 myocarditis via serpin A 3n.
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
Doxorubicin (Adriamycin) is an anthracycline chemotherapy agent effective in treating a wide range of malignancies1 with a well-established dose-response cardiotoxic side-effect that can lead to heart failure2-4. Even at relatively low cumulative doses of 200–250 mg/m2, the risk of cardiotoxicity is estimated at 7.8% to 8.8%4,5. Doxorubicin-induced cardiotoxicity (DIC) can range from asymptomatic reductions in left ventricular ejection fraction (LVEF) to highly symptomatic heart failure6,7. At present, it is not possible to predict which patients will be affected by DIC or adequately protect patients who are at risk for suffering this devastating side-effect8. Here we demonstrate that patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can recapitulate individual patients’ predilection to DIC at the single cell level. hiPSC-CMs derived from breast cancer patients who suffered clinical DIC are consistently more sensitive to doxorubicin toxicity, demonstrating decreased cell viability, mitochondrial/metabolic function, calcium handling, and antioxidant pathway gene expression, along with increased reactive oxygen species (ROS) production compared to hiPSC-CMs from patients who did not experience DIC. Together, our data indicate that hiPSC-CMs are a suitable platform for identifying and verifying the genetic basis and molecular mechanisms of DIC. Overall design: Comparision of the effect of 1uM doxorubicin for 24 h on gene expression in hiPSC-CM derived from 6 patients
Publication Title
Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray data on H9 hESC-derived cardiomyocytes (d30) treated with 0, 0.1, 1, or 10 uM of doxorubicin for 24 h
Publication Title
Human induced pluripotent stem cell-derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Rattus norvegicus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 4 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Determination of the mechanism by which fibrinogen, a central blood coagulation protein drives immunological responses targeted to the CNS. Results identify the factors involved in the regulation and provide mechanistic basis.
Publication Title
Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Determination of the mechanism by which fibrinogen, a central blood coagulation protein drives immunological responses targeted to the CNS. Results identify the factors involved in the regulation and provide mechanistic basis.
Publication Title
Blood coagulation protein fibrinogen promotes autoimmunity and demyelination via chemokine release and antigen presentation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
A key event in the pathogenic process of prion diseases is the conversion of the cellular prion protein (PrPC) to an abnormal and protease-resistant isoform (PrPSc). Mice lacking PrP are resistant to prion infection, and down-regulation of PrPC during prion infection prevents neuronal loss and the progression to clinical disease. These results are suggestive of the potential beneficial effect of silencing PrPC during prion diseases. However, the silencing of a protein that is widely expressed throughout the CNS could be detrimental to brain homeostasis. The physiological role of PrPC remains still unclear, but several putative functions have been proposed. Among these, several lines of evidence support PrPC function in neuronal development and maintenance.
Publication Title
Developmental influence of the cellular prion protein on the gene expression profile in mouse hippocampus.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 138 Downloadable Samples
- Illumina HiSeq 2500
Description
Skeletal muscle possesses a remarkable capacity to regenerate when injured, but when confronted with major traumatic injury resulting in volumetric muscle loss (VML), the regenerative process consistently fails. The loss of muscle tissue and function from VML injury has prompted development of a suite of therapeutic approaches but these strategies have proceeded without a comprehensive understanding of the molecular landscape that drives the injury response. Herein, we administered a VML injury in an established rodent model and monitored the evolution of the healing phenomenology over multiple time points using muscle function testing, histology, and expression profiling by RNA sequencing. The injury response was then compared to a regenerative medicine treatment using orthotopic transplantation of autologous minced muscle grafts (~1?mm3 tissue fragments). A chronic inflammatory and fibrotic response was observed at all time points following VML. These results suggest that the pathological response to VML injury during the acute stage of the healing response overwhelms endogenous and therapeutic regenerative processes. Overall, the data presented delineate key molecular characteristics of the pathobiological response to VML injury that are critical effectors of effective regenerative treatment paradigms. Overall design: RNA-Seq time couse of muscle volumetric muscle loss injury healing with controls
Publication Title
Multiscale analysis of a regenerative therapy for treatment of volumetric muscle loss injury.
Sample Metadata Fields
No sample metadata fields
View Samples