The type III RNase Dicer is responsible for the maturation and function of microRNA (miRNA) molecules in the cell. It is now well documented that Dicer and the fine-tuning of the miRNA gene network are important for neuronal integrity. However, the underlying mechanisms involved in neuronal death, particularly in the adult brain, remain poorly defined. Here, we show that absence of Dicer in the adult forebrain is accompanied by a mixed neurodegenerative phenotype. While neuronal loss is observed in the hippocampus, cellular shrinkage is predominant in the cortex. Interestingly, neuronal degeneration coincides with the hyperphosphorylation of endogenous tau at several epitopes previously associated with neurofibrillary pathology. Transcriptome analysis of enzymes involved in tau phosphorylation identified ERK1 as one of the candidate kinases responsible for this event in vivo. We further demonstrate that miRNAs belonging to the miR-15 family are potent regulators of ERK1 expression in mouse neuronal cells and co-expressed with ERK1/2 in vivo. Last, we show that miR-15a is specifically downregulated in Alzheimers disease brain. In sum, these results support the hypothesis that changes in the miRNA network may contribute to a neurodegenerative phenotype by affecting tau phosphorylation.
Genetic ablation of Dicer in adult forebrain neurons results in abnormal tau hyperphosphorylation and neurodegeneration.
Specimen part
View SamplesAn efficient innate immune recognition of the intracellular parasite T. cruzi is crucial for host protection against development of Chagas disease, which often leads to multiple organ damage, particularly the heart leading to cardiomyopathy. Mechanisms modulated by MyD88 have been shown to be necessary for resistance against T, cruzi infection. Recently, Nod-like receptors have been shown to play an important role as innate immune sensors, particularly as they relate to inflammasome function, caspase activation, and inflammatory cytokine production. In this study, we aimed to investigate the participation of innate immune responses in general, and inflammasomes in particular, in heart inflammation and cardiac damage upon infection with the T. cruzi parasite.
Apoptosis-associated speck-like protein containing a caspase recruitment domain inflammasomes mediate IL-1β response and host resistance to Trypanosoma cruzi infection.
Specimen part
View SamplesRNAseq analysis of BAFF in vitro-stimulated (6 hours) murine nfkb2fl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor NF-kB2 in BAFF-stimulated B cells. Overall design: Splenic B cells from 12-week old relfl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with BAFF. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-κB Transcription Factors RELB and NF-κB2 in B Cells.
Specimen part, Treatment, Subject
View SamplesRNAseq analysis of CD40 in vitro-stimulated (6 hours) murine nfkb2fl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor NF-kB2 in activated B cells. Overall design: Splenic B cells from 12-week old relfl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with anti-CD40 and anti-IgM. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Impairment of Mature B Cell Maintenance upon Combined Deletion of the Alternative NF-κB Transcription Factors RELB and NF-κB2 in B Cells.
Specimen part, Treatment, Subject
View SamplesRNA-seq analysis of murine eGFP+ relbfl/flnfkb2fl/flCg1-Cre and Cg1-Cre splenic germinal center B cells identifies genes regulated by the transcription factors RELB and p52 (NF-kB2) in germinal center B cells. Overall design: Germinal center B cells from 12-week old relbfl/flnfkb2fl/flCg1-Cre and Cg1-Cre littermate mice immunized with sheep red blood cells (SRBC) were isolated at day 7 after immunization by flow cytometric sorting from splenic mononuclear cells. RNA was isolated, amplified and submitted for RNA-sequencing on an Illumina HiSeq2500 instrument for 35-40 million 2x50 paired-ended reads.
Transcription factors of the alternative NF-κB pathway are required for germinal center B-cell development.
Age, Specimen part, Subject
View SamplesRNAseq analysis of CD40 + IgM in vitro-stimulated (6 hours) murine relafl/flCD19-Cre (furtheron designated as RELA) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor RELA in activated B cells. Overall design: Splenic B cells from 12-week old relafl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with anti-CD40 and anti-IgM. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits.
No sample metadata fields
View SamplesRNAseq analysis of CD40 + IgM in vitro-stimulated (6 hours) murine relfl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor c-REL in activated B cells. Overall design: Splenic B cells from 12-week old relfl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 6 hours with anti-CD40 and anti-IgM. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits.
No sample metadata fields
View SamplesRNAseq analysis of CD40 + IgM in vitro-stimulated (24 hours) murine relfl/flCD19-Cre (furtheron designated as REL) and CD19-Cre (furtheron designated as WT) splenic B cells identifies genes regulated by the transcription factor c-REL in activated B cells. Overall design: Splenic B cells from 12-week old relfl/flCD19-Cre and CD19-Cre littermate mice were isolated by magnetic cell separation from splenic mononuclear cells and stimulated in vitro for 24 hours with anti-CD40 and anti-IgM. RNA was isolated and submitted for RNA-sequencing on an Illumina HiSeq2000 instrument for 30 million single-ended reads.
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits.
No sample metadata fields
View SamplesGene expression profiling of murine eGFP+ relfl/flCg1-Cre and eGFP Cg1-Cre splenic germinal center B cells identifies genes regulated by the transcription factor c-REL in germinal center B cells.
Germinal center B cell maintenance and differentiation are controlled by distinct NF-κB transcription factor subunits.
Age, Specimen part, Time
View SamplesWe investigated gene expression signatures in subcutaneous adipose tissue obtained from control subjects, premanifest HD gene carriers and manifest HD subjects with the aim to identify gene expression changes and signalling pathway alterations in adipose tissue relevant to HD.
Analysis of White Adipose Tissue Gene Expression Reveals CREB1 Pathway Altered in Huntington's Disease.
Sex, Age
View Samples