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SRP082142
Mus musculus
8 Downloadable Samples
NextSeq 500
Description
The balance between protecting tissue integrity and efficient immune response is critical for host survival. Here we investigate the role of extracellular matrix (ECM) proteolysis in achieving this balance in the lung during influenza virus infection using a combined genomic and proteomic approach. We followed the transcriptional dynamics and ECM- related responses in a mouse model of influenza virus infection, integrated with whole tissue imaging and functional assays. Our study identifies MT1-MMP as a prominent host-ECM-remodeling collagenase in influenza virus infection. We show that selective inhibition of MT1-MMP-driven ECM proteolysis protects the tissue from infection-related structural and compositional damage. Inhibition of MT1-MMP did not significantly alter the immune response or cytokine expression, indicating its dominant role in ECM remodeling. We demonstrate that the available treatment for influenza virus (Tamiflu/ Oseltamivir) does not prevent lung ECM damage and is less effective than anti-MT1-MMP treatment in influenza virus and Streptococcus pneumoniae coinfection paradigms. Importantly, combination therapy of Tamiflu with anti-MT1-MMP shows a strong synergistic effect and results in complete recovery in mice. This study highlights the importance of tissue tolerance agents for surviving infectious diseases, and the potential of such host-pathogen therapy combination for respiratory infections. Overall design: Overall 8 samples were included, in duplicates, both infected and non-infected control cells were includeda. Both MT1-MMP positive and MT1-MMP negative were tested were non-infectdd, MT1-MMP negative cells served as controls.
Publication Title
Extracellular Matrix Proteolysis by MT1-MMP Contributes to Influenza-Related Tissue Damage and Mortality.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- NextSeq 500
Description
It is well established that the expression profiles of multiple and possibly redundant matrix remodeling proteases (e.g. collagenases) strongly differ in health, disease and development. Although enzymatic redundancy might be inferred from their close similarity in structure, their in-vivo activity can lead to extremely diverse tissue-remodeling outcomes. We observed that proteolysis of collagen-rich natural extracellular matrix (ECM), generated uniquely by individual homologous proteases, leads to specific combinatorial events, which eventually affects overall ECM topography, visco-elastic properties and composition. We reveal striking differences in the movement and signaling patterns, morphology, and gene expression profiles of cells interacting with natural collagen-rich ECM degraded by different collagenases. Thus, unlike envisioned before matrix-remodeling systems are not redundant and give rise to precise ECM-cell crosstalk. As ECM proteolysis is an abundant biochemical process critical to tissue homoeostasis, these results improve our fundamental understanding of combinatorial factors dictating cell behavior. Overall design: We analyzed the transcriptional responses of fibroblasts interacting with MMP1 or MMP13-remodeled ECM 4 hours post seeding. Samples used: Fibroblasts interacting with MMP1-remodeled ECM; Fibroblasts interacting with MMP13-remodeled ECM; Control samples- Fibroblasts interacting with natural ECM. All samples were run in duplicates.
Publication Title
Distinct biological events generated by ECM proteolysis by two homologous collagenases.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 7 Downloadable Samples
Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
In plants, many gene transcripts are very unstable, which is important for the tight control of their temporal and spatial expression patterns. To identify cellular factors controlling the stability of unstable mRNAs in plants, we used luciferase imaging in Arabidopsis to isolate a recessive mutant, stabilized 1 (sta1), with enhanced stability of the normally unstable luciferase transcript. The sta1 mutation also causes the stabilization of some endogenous gene transcripts and has a range of developmental and stress response phenotypes. STA1 encodes a nuclear protein similar to the human U5 snRNP-associated 102-kDa protein and to the yeast pre-mRNA splicing factor Prp1p and Prp6p. STA1 expression is up-regulated by cold stress, and the sta1 mutant is defective in the splicing of the cold-induced COR15A gene. Our results show that STA1 is a pre-mRNA splicing factor required for not only splicing but also the turnover of unstable transcripts and that it has an important role in plant responses to abiotic stresses.
Publication Title
STABILIZED1, a stress-upregulated nuclear protein, is required for pre-mRNA splicing, mRNA turnover, and stress tolerance in Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
ced1 mutant has reduced expression of NCED3 in response to osmotic stress (polyethylene glycol) treatments compared to the wild type. Other ABA biosynthesis genes are also greatly reduced in ced1 under osmotic stress.
Publication Title
The plant cuticle is required for osmotic stress regulation of abscisic acid biosynthesis and osmotic stress tolerance in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 1 Downloadable Sample
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Sin3a, a known master scaffold, provides unique contact surfaces for interaction with particular accessory proteins to repress the transcription of specific genes. Surprisingly, our results also suggest that Sin3a has a role in transcriptional activation.
Publication Title
Sin3a-Tet1 interaction activates gene transcription and is required for embryonic stem cell pluripotency.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Arabidopsis thaliana
- 2 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We carried out a microarray experiment by using Affymetrix Arabidopsis ATH1 Genechips in order to identify genes that show reduced expression in ros1-1 plants.
Publication Title
The DNA glycosylase/lyase ROS1 functions in pruning DNA methylation patterns in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 4 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
NFYA5 is a transcription factor important for drought resistance. Drought stress up-regulates NFYA5 gene expression not only at the transcriptional level but also at the posttranscriptional level by down-regulating the expression of miR169a that targets NFYA5 transcript for cleavage.
Publication Title
The Arabidopsis NFYA5 transcription factor is regulated transcriptionally and posttranscriptionally to promote drought resistance.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Upon virus infection, RIG-I-like receptors in host cells recognize viral RNA and activate type I interferon expression. To investigate the role of protein methylation in the anti-viral signaling pathway, we screened all the SET domain containing proteins and identified TTLL12 as a negative regulator of RIG-I signaling pathway. TTLL12 contains SET and TTL domains, which are predicted to have lysine methyltransferase and tubulin tyrosine ligase activities, respectively. Exogenous expression of TTLL12 represses IFN-ß expression induced by SeV. TTLL12 deficiency by RNA interference and CRISPR-gRNA techniques increases the induced IFN-ß expression and inhibits virus replication in the cell. Gene expression profiling also indicated that TTLL12 specifically inhibits the expression of the downstream genes of innate immunity pathways. Cell fractionation and fluorescent staining indicated that TTLL12 is localized in the cytosol. The study of various mutants suggested TTLL12's ability to repress RIG-I pathway is probably not dependent on protein modifications. Instead, TTLL12 directly interacts with VISA, TBK1 and IKKe, and inhibits the interactions of VISA with other signaling proteins. Taken together, our findings demonstrate TTLL12 as a negative regulator of RNA-virus-induced type I IFNs expression through inhibition of the interaction of VISA with other proteins. Overall design: TTLL12 was knocked down by siRNA in HCT116 and the gene expression profile was studied by RNA sequencing
Publication Title
TTLL12 Inhibits the Activation of Cellular Antiviral Signaling through Interaction with VISA/MAVS.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Primary cilium serves as a cellular antenna to sense environmental signals. Ciliogenesis requires the removal of CP110 to convert the mother centriole into the basal body. Actin dynamics is also critical for cilia formation. How these distinct processes are properly regulated remains unknown. Here we show that miR-129-3p, a microRNA conserved in the vertebrates, controlled cilia assembly by down-regulating both CP110 and four proteins critical for actin dynamics, Arp2, Toca1, abLIM1, and abLIM3. Consistently, blocking miR-129-3p repressed cilia formation in cultured mammalian cells, whereas its overexpression potently induced ciliogenesis in proliferating cells and extraordinary cilia elongation. Moreover, inhibition of miR-129-3p in zebrafish embryos suppressed cilia assembly in the Kupffers vesicle and pronephric duct, leading to developmental abnormalities including curved body, pericardial oedema, and randomised left-right patterning. Our results thus unravel a novel mechanism that orchestrates both the centriole-to-basal body transition and subsequent cilia assembly via microRNA-mediated posttranscriptional regulations.
Publication Title
miR-129-3p controls cilia assembly by regulating CP110 and actin dynamics.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To investigate Pten function in neonatal developing brain, we conditionally inactivated Pten in neural stem/progenitor cells at birth using a Nestin-CreER transgenic driver. Pten inactivation created a novel perivascular proliferative niche in the cerebellum that did not progress to malignancy during the lifespan of the mouse. Co-deletion of Pten and Trp53 synergized to cause fully penetrant medulloblastoma originating from a perivascular niche. The Pten and Trp53 double knock-out medulloblastomas showed an extensive and abnormal blood vessel network and advanced neuronal differentiation of tumor cells compared to medulloblastomas arising in Nestin-creER;Trp53fl/fl mice, suggesting that Pten loss promoted angiogenesis and neuronal differentiation in medulloblastoma. EdU pulse-chase experiments demonstrated a lineage hierarchy of the double knock-out medulloblastomas consistent with a perivascular cancer stem cell population. The Pten and Trp53 double knock-out medulloblastomas showed somatic loss of chromosomes 7, 13 and 16, and inactivating mutations in the tumor suppressor gene Ptch1. Gene expression profiles showed that this model recapitulated the subgroup of human medulloblastomas with de-regulated SHH signaling.
Publication Title
PTEN Signaling in the Postnatal Perivascular Progenitor Niche Drives Medulloblastoma Formation.
Sample Metadata Fields
Sex, Specimen part
View Samples