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GSE75960
Homo sapiens
23 Downloadable Samples
Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
Bromodomain and extra terminal domain (BET) inhibition reduces occupancy of BET-family proteins at promoter and enhancer sites resulting in changes in the transcription of specific genes.
Publication Title
Inhibition of BET bromodomain-dependent XIAP and FLIP expression sensitizes KRAS-mutated NSCLC to pro-apoptotic agents.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
Illumina HiSeq 2500
Description
Very little is known about splicing and its regulation in germ cells, particularly during meiosis. This paper describes the role of a male germ cell-specific protein, Tudor containing protein 6 (TDRD6), in assembly of the spliceosome in spermatocytes. We show that in spermatocytes, TDRD6 interacts with the key protein methyl transferase of the splicing pathway PRMT5. PRMT5 methylates arginines in substrate proteins. In a methylation dependent manner, TDRD6 also associates with spliceosomal core protein SmB in the absence of RNA, thus before an RNP-type spliceosome has been assembled. In Tdrd6-/- primary spermatocytes, PRMT5''s association with SmB and the arginine dimethylation of SmB are much reduced. Abrogation of arginine methylation impaired the assembly of spliceosomes and the presence of the spliceosomal RNA U5 is aberrantly increased. These deficiencies in spliceosome maturation correlated with decreased numbers of Cajal bodies and gems involved in later stages, i.e. nuclear snRNP maturation. To reveal functional consequences of these deficiencies, transcriptome analysis of primary spermatocytes showed high numbers of splicing defects such as aberrant usage of intron and exons as well as aberrant representation of splice junctions upon TDRD6 loss. This study reveals a novel function of TDRD6 in spliceosome maturation and mRNA splicing in spermatocytes. Overall design: Examination of splicing defects in isolated diplotene cells of 20dpp Tdrd6-/- vs. Tdrd6+/- testes pooled from at least 4 mice by deep sequencing in duplicate using Illumina® HiSeq 2500.
Publication Title
TDRD6 mediates early steps of spliceosome maturation in primary spermatocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
Identifying the signals that regulate the survival, lineage allocation and specification of pancreas progenitors will help elucidate the embryonic origins of pancreas dysfunction and provide important cues for the efficient conversion of pluripotent stem cells into fully functional ß cells. Several transcription factors regulating the conversion of the early pancreatic progenitors into terminally differentiated cells have been identified but extracellular signals regulating pancreas development are less well understood. Using a combination of genetic approaches, organotypic cultures of embryonic pancreata and genomics we have found that sphingosine-1-phosphate signalling through plays a key role in this process. S1p signalling stabilizes the Hippo pathway effector YAP to promote progenitor survival, acinar and endocrine specification. Endocrine cell specification relies on Gai subunits revealing an unexpected dependence of lineage specification on selected intracellular signalling components. Independently of YAP stabilization, S1p signalling attenuates Notch levels, thus regulating lineage allocation. These findings identify S1p signalling as a key pathway coordinating cell survival, lineage allocation and specification during pancreas development. Overall design: Analysis was carried out at 14.5 dpc embryonic pancreata and in 14.5 dpc embryonic pancreata that have been cultured in air to liquid interface cultures for two days (14.5 + 2). For the 14.5 dpc analysis wild type (14.5 wt) and S1pr2 null (14.5 S1pr2 null) pancreata were analyzed. For the analysis of cultured embryonic pancreata, conditions used were either standard conditions (14.5 + 2) or in the presence of 15 uM of JTE013 (14.5 + 2 + JTE) or in the presence of 15 uM of JTE013 and 50 ng/ml CTGF (14.5 + 2 + JTE + CTGF). Three biological replicates were used for each stage/condition for a total of 15 samples.
Publication Title
Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
The hematopoietic stem cell (HSC) compartment consists of a small pool of cells capable of replenishing all blood cells. Although it is established that the hematopoietic system is assembled as a hierarchical organization under steady-state conditions, emerging evidence suggests that distinct differentiation pathways may exist in response to acute stress. However, it remains unclear how different hematopoietic stem and progenitor cell subpopulations behave under sustained chronic stress. Here, by using adult transgenic mice over-expressing erythropoietin (EPO; Tg6) and a combination of in vivo, in vitro, and deep sequencing approaches, we found that HSCs respond differentially to chronic erythroid stress than their closely related multipotent progenitors (MPPs). Specifically, HSCs exhibit a vastly committed erythroid progenitor profile with enhanced cell division, while MPPs display erythroid and myeloid cell signatures and an accumulation of uncommitted cells. Thus, our results identify HSCs as master regulators of chronic stress erythropoiesis, potentially circumventing the hierarchical differentiation-detour. Overall design: HSC and MPP from WT or Tg mice were analyzed in triplicates.
Publication Title
Hematopoietic Stem Cells but Not Multipotent Progenitors Drive Erythropoiesis during Chronic Erythroid Stress in EPO Transgenic Mice.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 101 Downloadable Samples
- Illumina HiSeq 2500
Description
The experiment aimed at determing the influence of mast cell deficiency on the transcriptome of skin-infiltrating leukocytes in K14HPV16 mice at 2month and 6month of age. Overall design: Skin-inflitrating leucocytes were FACS-purified from mast cell proficient (Mcpt5-Cre-) and mast cell deficient (Mcpt5-Cre+) K14HPV16 mice. Mast cells (CD117 high, FCeR1 high) were excluded from the sorting gate. In order to control for minimal mast cell contamination during sorting from K14HPV16 Mcpt5-Cre- skin, mast cell signature transcripts were identified by comparing transcriptomes of samples fromK14HPV16 Mcpt5-Cre- mice in which mast cells were flow cytometrically included vs excluded.
Publication Title
Although Abundant in Tumor Tissue, Mast Cells Have No Effect on Immunological Micro-milieu or Growth of HPV-Induced or Transplanted Tumors.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 38 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA seq was used to compare the expression profile of macrophages in presence and absense of mast cells. MB49 cells were injected i.d. into Mcpt5-Cre+ R26DTA animals and cre-negative littermates. Macrophages were sorted at 20 d.p.i. Overall design: Macrophage RNA profiles of MB49 TAMs (tumor-associated macrophages), harvested at 20 d.p.i. in MC-Proficient and MC-deficient animals
Publication Title
Although Abundant in Tumor Tissue, Mast Cells Have No Effect on Immunological Micro-milieu or Growth of HPV-Induced or Transplanted Tumors.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
Transcriptome analysis of somatic stem cells and their progeny is fundamental to identify new factors controlling proliferation versus differentiation during tissue formation. Here we generated a combinatorial, fluorescent reporter mouse line to isolate proliferating neural stem cells, differentiating progenitors and newborn neurons that coexist as intermingled cell populations during brain development. Transcriptome sequencing revealed numerous novel long non-coding (lnc)RNAs and uncharacterized protein-coding transcripts identifying the signature of neurogenic commitment. Importantly, most lncRNAs overlapped neurogenic genes and shared with them a nearly identical expression pattern suggesting that lncRNAs control corticogenesis by tuning the expression of nearby cell fate determinants. We assessed the power of our approach by manipulating lncRNAs and protein-coding transcripts with no function in corticogenesis reported to date. This led to several evident phenotypes in neurogenic commitment and neuronal survival indicating that our study provides a remarkably high number of uncharacterized transcripts with hitherto unsuspected roles in brain development. Finally, we focussed on one lncRNA, Miat, whose manipulation was found to trigger pleiotropic effects on brain development and aberrant splicing of Wnt7b. Hence, our study suggests that lncRNA-mediated alternative splicing of cell fate determinants controls stem cell commitment during neurogenesis. “LncRNAs control neurogenesis” Aprea, Prenninger, Dori, Monasor, Wessendof, Zocher, Massalini, Ghosh, Alexopoulou, Lesche, Dahl, Groszer, Hiller, Calegari, The EMBO Journal (In Press) Overall design: mRNA profiles of Proliferating Progenitors, Differentiating Progenitors and Neurons from lateral cortex of E14.5 mouse embryos. Each cell type in three biological replicates.
Publication Title
Transcriptome sequencing during mouse brain development identifies long non-coding RNAs functionally involved in neurogenic commitment.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Biallelic defects of the gene encoding for the intracellular enzyme 3’ repair exonuclease (Trex)1 cause Aicardi-Goutières syndrome (AGS), a rare monogenic, lupus-like autoimmune disease, while heterozygous Trex1 loss of function alleles are associated with systemic lupus erythematosus (SLE). Trex1-/- mice develop lethal autoimmune multi-organ inflammation, which results from a chronic type I IFN response triggered by intracellular accumulation of a putative nucleic acid substrate of Trex1. This pathogenic nucleic acid is detected by the broadly, but not ubiquitously, expressed cytosolic DNA sensor cGAS, raising the question whether there are specific cell types that respond to Trex1 deficiency by production of IFN and induce autoimmunity. We generated mice with conditional knock out of the Trex1 gene and demonstrated that loss of Trex1 throughout the hematopoietic system and even selective loss in dendritic cells is sufficient to cause IFN release and autoimmunity. B cells showed no transcriptional response to Trex1 deficiency. Trex1-/- keratinocytes produced IFN but did not induce skin inflammation, whereas loss of Trex1 in cardiomyocytes triggered neither IFN response nor pathology. Trex1-deficient neurons and astrocytes did not release IFN in the CNS. In contrast, mice with selective inactivation of Trex1 in long-living CNS macrophages such as microglia locally produced IFN but did not reproduce the mild encephalitis seen in Trex1-/- mice. Collectively, individual cell types differentially respond to the loss of Trex1 and dendritic cells seem promising candidates for experiments addressing the molecular pathomechanism in Trex1 deficiency. Overall design: We sorted CD19-positive B cells from spleens of Trex1fl/fl CD19-Cre+ and Trex1fl/fl CD19-Cre- mice and isolated total RNA for library construction to perform mRNA deep sequencing.
Publication Title
Loss of Trex1 in Dendritic Cells Is Sufficient To Trigger Systemic Autoimmunity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The amygdala is a prominent region of the brain processing stress-related emotion and vigilance. Additionally it is known that the serotonergic system is strongly involved in stress response and adaptation. The serotonin transporter (5-HTT) as key regulator of serotonergic activity in the brain is associated with stress-related neuropsychiatric disorders as well as heightened trait anxiety/dysphoria and exaggerated response to fear and environmental stress in humans. Also 5-HTT knockout mice display increased anxiety- and depression-related behaviors, altered stress reactivity and stress-coping abilities, gene expression differences and altered dendritic morphology.
Publication Title
Effect of acute stressor and serotonin transporter genotype on amygdala first wave transcriptome in mice.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Rattus norvegicus
- 28 Downloadable Samples
- Affymetrix Rat Gene 2.1 ST Array (ragene21st)
Description
We aimed to characterize the complex cardiovascular effects of NOsGC stimulation using NO-independent stimulator BAY 41-8543 in a double transgenic rat (dTGR) model of HFpEF.
Publication Title
Nitric oxide-sensitive guanylyl cyclase stimulation improves experimental heart failure with preserved ejection fraction.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples