Transcription factor pancreatic and duodenal homeobox 1 (Pdx1) plays an essential role in the pancreas to regulate its development and maintain proper islet function. However, less is known about the function of Pdx1 in the small intestine.
Expression profiling identifies novel gene targets and functions for Pdx1 in the duodenum of mature mice.
Sex, Age
View SamplesThe normally virulent type-I RH parasite is rendered avirulent when lacking ROP5. The avirulent phenotype is a consequence of interaction with the host innate immune system. We sought to understand if ROP5 alters host gene expression in order to escape host defenses. We saw no gene expression differences between host cells infected with wt (RHku80) or RHku80rop5 parasites. We have included uninfected HFF samples that were harvested in parallel with the infected samples.
The polymorphic pseudokinase ROP5 controls virulence in Toxoplasma gondii by regulating the active kinase ROP18.
Specimen part
View SamplesPolycomb repressive complex 2 (PRC2) maintains developmental regulator genes in a repressed state through methylation of histone H3 at lysine 27 (H3K27me3) and is necessary for cell differentiation. We and others have previously found that the PRC2 subunit Suz12 interacts with RNA in vitro and other studies have shown that Ezh2 and Jarid2 also possess RNA binding function. The interaction of PRC2 with RNA has been suggested to regulate PRC2 targeting or enzymatic activity, but the RNAs directly bound by PRC2 in cells, and the role of each PRC2 RNA binding subunit, remain unclear. We have used different CLIP techniques, which use UV-crosslinking to allow detection of direct Suz12-RNA interactions as they occur in living mouse ES cells. Suz12 binds nascent RNA and has a preference for interaction with the 3'UTR, showing it does have binding specificity in cells. RNAs bound by Suz12 at the 3'UTR encode developmental regulator genes. Suz12 remains bound to RNA upon deletion of Ezh2 or Jarid2 showing that it binds RNA independently of other PRC2 subunits. We also show that binding of Suz12 to RNA or chromatin is mutually inhibitory. Although Ezh2 and Jarid2 also bind RNA, Ezh2 and Jarid2 deletion causes an increase in Suz12 RNA binding, without changing its specificity, which reflects the loss of Suz12 from chromatin. Similarly, disruption of Suz12-RNA interactions by RNA polymerase II inhibition or RNase treatment increases Suz12 binding to chromatin. These results therefore suggest that Suz12 acts as an RNA sensor, binding to the 3'UTR of nascent RNAs and modulating the interaction of PRC2 with chromatin. Overall design: Total RNAseq libraires from of Mus musculus Ezh2 fl/fl Stem Cells after and before Tamoxifen treatment.Up to three replicates per condition
The interaction of PRC2 with RNA or chromatin is mutually antagonistic.
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View SamplesRetention of lymphocytes in the intestinal mucosa requires specialized chemokine receptors and adhesion molecules. Here we find that both CD4+CD8+ and CD4+T cells in the intestinal epithelium, as well as CD8+T cells in the intestinal mucosa and mesenteric lymph nodes, express the cell adhesion molecule Crtam upon activation, whereas the ligand of Crtam, Cadm1, is expressed on gut CD103+DCs. Lack of Crtam-Cadm1 interactions in Crtam-/- and Cadm1-/- mice results in loss of CD4+CD8+T cells, which arise from mucosal CD4+T cells that acquire a CD8 lineage expression profile. Following acute oral infection with T. gondii, both WT and Crtam-/- mice mounted a robust TH1 response, but markedly fewer TH17 cells were present in the intestinal mucosa of Crtam-/- mice. The almost exclusive TH1 response in Crtam-/- mice resulted in more efficient control of intestinal T. gondii infection.
CRTAM controls residency of gut CD4+CD8+ T cells in the steady state and maintenance of gut CD4+ Th17 during parasitic infection.
Specimen part, Treatment, Time
View SamplesAstrocyte responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanism that determines these different responses are poorly understood. Transcriptional analysis showed that EphB1 induces a protective inflammatory signature in astrocytes, which is distinct from the response evoked by interleukin (IL)-6, which is known to have both pro- and anti-inflammatory properties. We demonstrate that this beneficial EphB1 induced signaling pathway is disrupted in astrocytes derived from human induced pluripotent stem cells (iPSC) of amyotrophic lateral sclerosis (ALS) patients. Overall design: Examination of transcriptome-wide gene expression profiles of purified murine wildtype astrocyte cultures (untreated and treated with IL-6 or EphB1).
A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models.
Specimen part, Cell line, Subject
View SamplesAstrocyte responses to neuronal injury may be beneficial or detrimental to neuronal recovery, but the mechanism that determines these different responses are poorly understood. Transcriptional analysis showed that EphB1 induces a protective inflammatory signature in astrocytes, which is distinct from the response evoked by interleukin (IL)-6, which is known to have both pro- and anti-inflammatory properties. We demonstrate that this beneficial EphB1 induced signaling pathway is disrupted in astrocytes derived from human induced pluripotent stem cells (iPSC) of amyotrophic lateral sclerosis (ALS) patients. Overall design: Examination of transcriptome-wide gene expression profiles of terminally differentiated and enriched iPSC-derived astrocytes harboring the SOD1 D90A mutation
A neuroprotective astrocyte state is induced by neuronal signal EphB1 but fails in ALS models.
Specimen part, Subject
View SamplesWe used Illumina-HiSeq4000 to sequence 4sU-labelled RNA samples isolated from unchallenged and DNA damaged HeLa Flp-In cells, which revealed the nature of transcriptional response folowing genotoxic stress and the contribution of P-TEFb kinase in DNA damage-induced gene transcription. Overall design: We mock treated or treated HeLa Flp-In cells for 1 or 2 hr with DMSO, 4-NQO, or 4-NQO + flavopiridol (FP) as indicated below. During the last 30 minutes of the treatments, we labeled the RNA or not with the nucleoside analogue 4-thiouridine (500µM 4sU) for 30 minutes.
P-TEFb Activation by RBM7 Shapes a Pro-survival Transcriptional Response to Genotoxic Stress.
Cell line, Subject
View SamplesBatf3 regulates key CD8alpha DC-specific genes.
Compensatory dendritic cell development mediated by BATF-IRF interactions.
Specimen part
View SamplesDiagnosis of inflamed human orbit tissue with standard clinical and histopathology evaluation data is imprecise. A large number of these patients are diagnosed with the catch-all classification of nonspecific orbital inflammation (NSOI).
Orbital pseudotumor can be a localized form of granulomatosis with polyangiitis as revealed by gene expression profiling.
Sex, Specimen part, Disease
View SamplesDiagnosis of inflamed human lacrimal gland with standard clinical and histopathology evaluation data is imprecise. A large number of these patients are diagnosed with the catch-all classification of nonspecific orbital inflammation (NSOI).
Gene Expression Profiling and Heterogeneity of Nonspecific Orbital Inflammation Affecting the Lacrimal Gland.
Sex, Specimen part, Disease
View Samples