A study of diabetic neuropathy in dorsal root ganglia from streptozotocin-diabetic male wistar rats over the first 8 weeks of diabetes
Identification of changes in gene expression in dorsal root ganglia in diabetic neuropathy: correlation with functional deficits.
Sex, Age, Specimen part, Disease, Disease stage, Time
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Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP.
Cell line
View SamplesTo assess whether the transcripts identified by PAR-CLIP are regulated by the RNA-binding protein (RBP) Quaking (QKI), we analyzed the mRNA levels of mock-transfected and QKI-specific siRNA-transfected cells with microarrays. Transcripts crosslinked to QKI were significantly upregulated upon siRNA transfection, indicating that QKI negatively regulates bound mRNAs (Figure 3H of PMID 20371350), consistent with previous reports of QKI being a repressor.
Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP.
Cell line
View SamplesTo test the influence of IGF2BPs on the stability of their interacting mRNAs, as reported previously for some targets (Yisraeli, 2005), we simultaneously depleted all three IGF2BP family members using siRNAs and compared the cellular RNA from knockdown and mock-transfected cells on microarrays. The levels of transcripts identified by PAR-CLIP decreased in IGF2BP-depleted cells, indicating that IGF2BP proteins stabilize their target mRNAs. Moreover, transcripts that yielded clusters with the highest T to C mutation frequency were most destabilized (Figure 4G of PMID 20371350), indicating that the ranking criterion that we derived based on the analysis of PUM2 and QKI data generalizes to other RNA-binding proteins (RBPs).
Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP.
Cell line
View SamplesTo obtain evidence that Argonaute (AGO) crosslink-centered regions (CCRs) indeed contain functional miRNA-binding sites, we blocked 25 of the most abundant miRNAs in HEK 293 cells (Figure 5C of PMID 20371350) by transfection of a cocktail of 2'-O-methyl-modified antisense oligoribonucleotides and monitored the changes in mRNA stability by microarrays (Figure 7A of PMID 20371350). Consistent with previous studies of individual miRNAs (Grimson et al., 2007), the magnitude of the destabilization effects of transcripts containing at least one CCR depended on the length of the seed-complementary region and dropped from 9-mer to 8-mer to 7-mer to 6-mer matches (Figure 7B of PMID 20371350). We did not find evidence for significant destabilization of transcripts that only contained imperfectly paired seed regions.
Transcriptome-wide identification of RNA-binding protein and microRNA target sites by PAR-CLIP.
Cell line
View SamplesChanges in gene expression on MNV infection of RAW264.7 cells
Murine norovirus replication induces G0/G1 cell cycle arrest in asynchronously growing cells.
Cell line
View SamplesIn this study, we have utilized microarray analysis to directly compare a subset of structurally distinct, clinically relevant SERMs in the presence and absence of estradiol, using a high replicate number (10) to ensure detection of modestly regulated genes.
Research resource: Transcriptional profiling in a cellular model of breast cancer reveals functional and mechanistic differences between clinically relevant SERM and between SERM/estrogen complexes.
Cell line
View SamplesIn order to validate the utility of a novel pathway algorithm (BD-Func), we test if an LBH589 signature based data from 3 cell lines (GSE36509) in an independent experiment in vivo.
BD-Func: a streamlined algorithm for predicting activation and inhibition of pathways.
Specimen part, Treatment
View SamplesWe developed a technique for generating hypothalamic neurons from human pluripotent stem cells. Here, as proof-of-principle, we examine the use of these cells in modeling of a monogenic form of severe obesity: PCSK1 deficiency. We generated PCSK1 (PC1/3)-deficient human embryonic stem cell (hESC) lines using both shRNA and CRISPR-Cas9, and investigated pro-opiomelanocortin (POMC) processing using hESC-differentiated hypothalamic neurons. Overall design: We tried to idenitify transcripitional profiles and specific transcription factors that involved in of different stages during hypothalamic neuron differentiation from single cell sequencing for hESC-derived Day27 hypothalamic neurons, Day 12 neuron progenitors and undifferentiated stem cells
PC1/3 Deficiency Impacts Pro-opiomelanocortin Processing in Human Embryonic Stem Cell-Derived Hypothalamic Neurons.
Sex, Specimen part, Subject
View SamplesStaphylococcus aureus pneumonia causes significant morbidity and mortality. Alpha-hemolysin (Hla), a pore-forming cytotoxin of S. aureus, has been identified through animal models of pneumonia as a critical virulence factor that induces lung injury. In spite of considerable molecular knowledge of how this cytotoxin injures the host, the precise host response to Hla in the context of infection remains poorly understood. We employed whole-genome expression profiling of infected lung to define the host response to wild-type S. aureus compared with an Hla-deficient isogenic mutant in experimental pneumonia. These data provide a complete expression profile at four and at twenty-four hours post-infection, revealing a unique response to the toxin-expressing strain. Gene ontogeny analysis revealed significant differences in the extracellular matrix and cardiomyopathy pathways, both of which govern cellular interactions in the tissue microenvironment. Evaluation of individual transcript responses to Hla-secreting bacteria was notable for upregulation of host cytokine and chemokine genes, including the p19 subunit of interleukin-23. Consistent with this observation, the cellular immune response to infection was characterized by a prominent TH17 response to wild-type staphylococci. These findings define specific host mRNA responses to Hla-producing S. aureus, coupling the pulmonary TH17 response to the presence of this cytotoxin. Expression profiling to define the host response to a single virulence factor proved to be a valuable tool in identifying pathways for further investigation in S. aureus pneumonia. This approach may be broadly applicable to the study of bacterial toxins, defining host pathways that can be targeted to mitigate toxin-induced disease.
Host response signature to Staphylococcus aureus alpha-hemolysin implicates pulmonary Th17 response.
Sex, Specimen part
View Samples