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GSE68842
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Increasing evidence suggests that Long non-coding RNAs (LncRNAs) represent a new class of regulators of stem cells. However, the roles of LncRNAs in stem cell maintenance and myogenesis remain largely unexamined. For this study, hundreds of novel intergenic LncRNAs were identified that are expressed in myoblasts and regulated during differentiation. One of these LncRNAs, termed LncMyoD, is encoded next to the Myod gene and is directly activated by MyoD during myoblast differentiation. Knockdown of LncMyoD strongly inhibits terminal muscle differentiation largely due to a failure to exit the cell cycle. LncMyoD directly binds to IGF2-mRNA-binding-protein 2 (IMP2) and negatively regulates IMP2-mediated translation of proliferation genes such as N-Ras and c-Myc. While the RNA sequence of LncMyoD is not well-conserved between human and mouse, its locus, gene structure and function is preserved. The MyoD-LncMyoD-IMP2 pathway elucidates a mechanism as to how MyoD blocks proliferation to create a permissive state for differentiation.
Publication Title
A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Streptococcus suis is a major swine pathogen that can be transmitted to humans causing severe symptoms. A large human outbreak was described in China, where approximately 25% out of 215 infected humans developed an unusual streptococcal toxic shock-like syndrome (STSLS). Albeit increased expression of inflammatory mediators following infection by the Chinese S. suis strain was suggested as responsible for STSLS case severity, the mechanisms involved are still poorly understood. In this study, we investigated the host innate immune response to infection by either one of 3 strains of S. suis: 89-1591 (Canadian, intermediate virulence), P1/7 (European, high virulence), and SC84 (Chinese, epidemic strain). Using Illumina microarray and validating those results with qPCR and Luminex assay, infected mice showed elevated expression of mainly pro-inflammatory chemokine and cytokine genes. Generally, pro-inflammatory genes were expressed at a higher level in mice infected with S. suis strain SC84 > P1/7 > 89-1591. Interestingly, IFN was expressed at much higher levels only in mice infected with the S. suis strain SC84, which could potentially explain some of the STSLS symptoms. IFN-KO mice infected with SC84 showed better survival than WT mice while no differences was seen in mice infected with highly virulent P1/7 strain. Overall, our results show an important role of IFN in S. suis infections and might explain in part the increased virulence of SC84 responsible for a recent outbreak in China.
Publication Title
Exacerbated type II interferon response drives hypervirulence and toxic shock by an emergent epidemic strain of Streptococcus suis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Streptococcus suis is a major swine pathogen that can be transmitted to humans causing severe symptoms. A large human outbreak was described in China, where approximately 25% out of 215 infected humans developed an unusual streptococcal toxic shock-like syndrome (STSLS). Albeit increased expression of inflammatory mediators following infection by the Chinese S. suis strain was suggested as responsible for STSLS case severity, the mechanisms involved are still poorly understood. In this study, we investigated the host innate immune response to infection by either one of 3 strains of S. suis: 89-1591 (Canadian, intermediate virulence), P1/7 (European, high virulence), and SC84 (Chinese, epidemic strain). Using Illumina microarray and validating those results with qPCR and Luminex assay, infected mice showed elevated expression of mainly pro-inflammatory chemokine and cytokine genes. Generally, pro-inflammatory genes were expressed at a higher level in mice infected with S. suis strain SC84 > P1/7 > 89-1591. Interestingly, IFN was expressed at much higher levels only in mice infected with the S. suis strain SC84, which could potentially explain some of the STSLS symptoms. IFN-KO mice infected with SC84 showed better survival than WT mice while no differences was seen in mice infected with highly virulent P1/7 strain. Overall, our results show an important role of IFN in S. suis infections and might explain in part the increased virulence of SC84 responsible for a recent outbreak in China.
Publication Title
Exacerbated type II interferon response drives hypervirulence and toxic shock by an emergent epidemic strain of Streptococcus suis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Streptococcus suis is a major swine pathogen that can be transmitted to humans causing severe symptoms. A large human outbreak was described in China, where approximately 25% out of 215 infected humans developed an unusual streptococcal toxic shock-like syndrome (STSLS). Albeit increased expression of inflammatory mediators following infection by the Chinese S. suis strain was suggested as responsible for STSLS case severity, the mechanisms involved are still poorly understood. In this study, we investigated the host innate immune response to infection by either one of 3 strains of S. suis: 89-1591 (Canadian, intermediate virulence), P1/7 (European, high virulence), and SC84 (Chinese, epidemic strain). Using Illumina microarray and validating those results with qPCR and Luminex assay, infected mice showed elevated expression of mainly pro-inflammatory chemokine and cytokine genes. Generally, pro-inflammatory genes were expressed at a higher level in mice infected with S. suis strain SC84 > P1/7 > 89-1591. Interestingly, IFN was expressed at much higher levels only in mice infected with the S. suis strain SC84, which could potentially explain some of the STSLS symptoms. IFN-KO mice infected with SC84 showed better survival than WT mice while no differences was seen in mice infected with highly virulent P1/7 strain. Overall, our results show an important role of IFN in S. suis infections and might explain in part the increased virulence of SC84 responsible for a recent outbreak in China.
Publication Title
Exacerbated type II interferon response drives hypervirulence and toxic shock by an emergent epidemic strain of Streptococcus suis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 477 Downloadable Samples
Illumina HiSeq 2500
Description
Neuronal diversity is a defining feature of the mammalian brain deemed necessary for realizing the complex function of the nervous system. In order to begin to understand the transcriptional basis of this diversity, we collected more than 170 neuronal and non-neuronal cell type-specific transcriptomes defined operationally by transgenic mouse lines and anatomical regions. The dataset indicates that the genes specifically expressed in neuronal cell types are biased toward long genes. We revealed that these long genes have higher capacities to be differentially expressed between cell types and thus assume an important role in diversification of the neuronal transcriptomes. Since mobile element insertions are the main cause of the gene elongations, we propose that exaptation of the inserted mobile elements significantly contributed to the neuronal diversity. Overall design: Examination of whole cell transcriptomes in 174 cell types.
Publication Title
Mapping the transcriptional diversity of genetically and anatomically defined cell populations in the mouse brain.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 49 Downloadable Samples
- NextSeq 500
Description
Determination of the molecular properties of genetically targeted cell types has led to fundamental insights into mouse brain function and dysfunction. Here, we report an efficient strategy for precise exploration of gene expression events in specific cell types in a broad range of species. We demonstrate that classically defined, homologous neuronal and glial cell types differ between rodent and human by the expression of hundreds of orthologous, cell specific genes. Confirmation that these genes are differentially active was obtained using epigenetic mapping, quantitative PCR, and immunofluorescence localization. Studies of sixteen human postmortem brains revealed cell-specific molecular responses to aging, and the induction of a shared, robust response to an unknown external event experienced by three donors. Our data establish a comprehensive approach for analysis of unique molecular events associated with specific circuits and cell types in a wide variety of human conditions. Overall design: RNA purified from nuclei or cytoplasm from mouse, rat, or human cerebellum. ATAC-seq was also performed using cerebellar nuclei from the three species.
Publication Title
Species and cell-type properties of classically defined human and rodent neurons and glia.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Mus musculus
- 29 Downloadable Samples
- Illumina HiSeq 2500, NextSeq 500
Description
Determination of the molecular properties of genetically targeted cell types has led to fundamental insights into mouse brain function and dysfunction. Here, we report an efficient strategy for precise exploration of gene expression events in specific cell types in a broad range of species. We demonstrate that classically defined, homologous neuronal and glial cell types differ between rodent and human by the expression of hundreds of orthologous, cell specific genes. Confirmation that these genes are differentially active was obtained using epigenetic mapping, quantitative PCR, and immunofluorescence localization. Studies of sixteen human postmortem brains revealed cell-specific molecular responses to aging, and the induction of a shared, robust response to an unknown external event experienced by three donors. Our data establish a comprehensive approach for analysis of unique molecular events associated with specific circuits and cell types in a wide variety of human conditions. Overall design: RNA purified from nuclei or cytoplasm from mouse, rat, or human cerebellum. ATAC-seq was also performed using cerebellar nuclei from the three species.
Publication Title
Species and cell-type properties of classically defined human and rodent neurons and glia.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The recent interest in the role of bone marrow derived endothelial progenitor cells in the benefits of estrogen on cardiovascular health brought us to evaluate if estrogen could affect cardiac repair more broadly by regulating biological processes involved in the functional organization of the bone marrow stem cell niche.
Publication Title
Estrogen-induced gene expression in bone marrow c-kit+ stem cells and stromal cells: identification of specific biological processes involved in the functional organization of the stem cell niche.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Fusion of the EWS gene to FLI1 produces a fusion oncoprotein that drives an aberrant gene expression program responsible for the development of Ewing sarcoma. We used a homogenous proximity assay to screen for compounds that disrupt the binding of EWS-FLI1 to its cognate DNA targets. A number of DNA-binding chemotherapeutic agents were found to non-specifically disrupt protein binding to DNA. In contrast, actinomycin D was found to preferentially disrupt EWS-FLI1 binding by comparison to p53 binding to their respective cognate DNA targets in vitro. In cell-based assays, low concentrations of actinomycin preferentially blocked EWS-FLI1 binding to chromatin, and disrupted EWS-FLI1-mediated gene expression. Higher concentrations of actinomycin globally repressed transcription. These results demonstrate that actinomycin preferentially disrupts EWS-FLI1 binding to DNA at selected concentrations. Although the window between this preferential effect and global suppression is too narrow to exploit in a therapeutic manner, these results suggest that base-preferences may be exploited to find DNA-binding compounds that preferentially disrupt subclasses of transcription factors.
Publication Title
Differential disruption of EWS-FLI1 binding by DNA-binding agents.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- NextSeq500
Description
Loss-of-function studies are fundamental for dissecting gene function. Yet, methods to rapidly and effectively perturb genes in mammalian cells are scarce. We present a novel system, deliverable with only two lentiviral vectors, which enables simultaneous control over two different proteins in the same cell. By harnessing the plant auxin and jasmonate hormone-induced degradation pathways, combined with RNA interference, this system allows constitutive depletion of two endogenous proteins and their replacement with two exogenous proteins whose degradation is rapidly and reversibly induced by external ligands, representing a dual analog molecular tuner. Focusing on NANOG, CHK1 and NOTCH1 in embryonic stem cells and p53 in cancer cells we have validated the efficiency, rapidity, reversibility, titratability and multiplicity of the engineered tuners, and demonstrated their potential to facilitate previously-unfeasible experimental approaches and to generate novel biological insights. Overall design: For mRNA-Seq preparation, coronatine/DMSO treated cells were collected.
Publication Title
A dual molecular analogue tuner for dissecting protein function in mammalian cells.
Sample Metadata Fields
No sample metadata fields
View Samples