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GSE51691
Caenorhabditis elegans
11 Downloadable Samples
Affymetrix C. elegans Genome Array (celegans)
Description
Males induce dramatic physiological changes to hermaphrodites, including a significant shortening of lifespan. We have termed this effect as male-induced demise (MID) of hermaphrodites. This experiment was performed to analyse changes in gene expression due to the presence of males. We have shown that Knock down of utx-1 ameliorates the MID. In this experiment we also examine male-induce gene expression that may be altered when knocking down expression of utx-1 via RNAi.
Publication Title
Males shorten the life span of C. elegans hermaphrodites via secreted compounds.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 62 Downloadable Samples
NextSeq 500
Description
This study examines the transcriptional changes invoked by activation of gp130 signaling in different mouse models of B cell lymphomagenesis. In order to study the in vivo effects of aberrant activity of IL-6/IL-6R/gp130-JAK/STAT3 signaling, we designed a transgene that allows conditional expression of L-gp130 by generating a ROSA26 knock-in mouse strain where compound L-gp130 and ZsGreen expression from the CAG promoter is prevented by a loxP- and a rox-flanked stop cassette. Total RNA extracted from purified B cells from young CD19Cre+/- ;L-gp130fl/+ and wildtype control mice was sequenced using unique molecular identifiers (UMI) in a paired end design where read1 corresponds to the cDNA and read2 contains the UMI. Furthermore, aging CD19Cre+/- ;L-gp130fl/+ animals developed tumors located predominantly in mesenteric lymph nodes. Infiltration of CD19;L-gp activated B cells was determined by Flow Cytometry and ZsGreen expression. Total RNA from tumors generally containing >60% ZsGreen+ cells was profiled as described above, for tumors with lower CD19;L-gp activated B cell content FACS was applied. In order to study the effects of activated IL-6/IL-6R/gp130-JAK/STAT3 signaling on Eµ-Myc-driven lymphomagenesis, CD19Cre;L-gp130fl;Eµ-Myc triple transgenic mice were generated and fetal liver hematopoietic stem/progenitor cell (FL-HSPC) grafts were transplanted into lethally irradiated syngeneic mice alongside FL-HSPC from CD19Cre;L-gp130f and Eµ-Myc control mice. Lastly, IL-6/IL-6R/gp130-JAK/STAT3 signaling was activated in the entire hematopoetic system using Vav1Cre resulting in Vav1Cre+/- ;L-gp130fl/+ animals. Independent of the time point of activation during hematopoietic and B cell differentiation, all Cre;L-gp compound mice succumbed to tumors of B cell origin. Overall design: Bulk gene expression data are presented for (i) purified B cells from wildtype control mice (n=6) and young CD19;L-gp mice (n=4), (ii) tumors detected in aging CD19;L-gp mice with a mature (n=11) and plasma cell phenotype (n=6), respectively, (iii) tumors arising in lethally irradiated syngeneic mice after transplantation of fetal liver hematopoietic stem/progenitor cells from CD19;L-gp;Myc (n=9), CD19;L-gp (n=7) and Eµ-Myc (n=9) mice, respectively, and (iv) malignant B cells from Vav1;L-gp mice (n=13).
Publication Title
Activated gp130 signaling selectively targets B cell differentiation to induce mature lymphoma and plasmacytoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Danio rerio
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Identification of genes that are differentially-expressed in dusp2um287/um287;dusp6um286/um286 mutant embryos compared to wildtype Overall design: Total RNA was extracted from pools of dechrionated, deyolked wildtype and dusp2um287/um287;dusp6um286/um286 embryos at 18hpf using the RNeasy Mini Kit (Qiagen). Three libraries from wildtype embryos and three libraries from dusp2um287/um287;dusp6um286/um286 embryos were then generated from 3mg RNA using the TruSeq Stranded mRNA Library Prep Kit (Illumina). All libraries were analyzed for quality on a bioanalyzer prior to sequencing (Agilent 2100 BioAnalyzer).
Publication Title
A parental requirement for dual-specificity phosphatase 6 in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 35 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Chromatin modifiers regulate lifespan in several organisms, raising the question of whether changes in chromatin states in the parental generation could be incompletely reprogrammed in the next generation and thereby affect the lifespan of descendents. The histone H3 lysine 4 trimethylation (H3K4me3) complex composed of ASH-2, WDR-5, and the histone methyltransferase SET-2 regulates C. elegans lifespan. Here we show that deficiencies in the H3K4me3 chromatin modifiers ASH-2, WDR-5, or SET-2 in the parental generation extend the lifespan of descendents up until the third generation. The transgenerational inheritance of lifespan extension by members of the ASH-2 complex is dependent on the H3K4me3 demethylase RBR-2, and requires the presence of a functioning germline in the descendents. Transgenerational inheritance of lifespan is specific for the H3K4me3 methylation complex and is associated with epigenetic changes in gene expression. Thus, manipulation of specific chromatin modifiers only in parents can induce an epigenetic memory of longevity in descendents.
Publication Title
Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
identification of differentially expressed genes in gas6 homozygous mutant hindbrain when compared to wildtype hindbrain in zebrafish Overall design: Total RNA was extracted from dissected hindbrain of gas6 homzygous mutants and wildtype embryos at 48hpf using the RNeasy Mini Kit (Qiagen). Three libraries from wildtype embryos and three libraries from gas6 mutants were then generated from 3mg RNA using the TruSeq Stranded mRNA Library Prep Kit (Illumina). All libraries were analyzed for quality on a bioanalyzer prior to sequencing (Agilent 2100 BioAnalyzer).
Publication Title
Analysis of novel caudal hindbrain genes reveals different regulatory logic for gene expression in rhombomere 4 versus 5/6 in embryonic zebrafish.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Alveolar epithelial type II (ATII)-like cells can be generated from murine embryonic stem cells (ESCs), although to date, no robust protocols applying specific differentiation factors are established. We hypothesized that the keratinocyte growth factor (KGF), an important mediator of lung organogenesis and primary ATII cell maturation and proliferation, together with dexamethasone, 8-bromoadenosine-cAMP, and isobutylmethylxanthine (DCI), which induce maturation of primary fetal ATII cells, also support the alveolar differentiation of murine ESCs. Here we demonstrate that the above stimuli synergistically potentiate the alveolar differentiation of ESCs as indicated by increased expression of the surfactant proteins (SP-) C and SP-B. This effect is most profound if KGF is supplied not only in the late stage, but at least also during the intermediate stage of differentiation. Our results indicate that KGF most likely does not enhance the generation of (mes)endodermal or NK2 homeobox 1 (Nkx2.1) expressing progenitor cells but rather, supported by DCI, accelerates further differentiation/maturation of respiratory progeny in the intermediate phase and maturation/proliferation of emerging ATII cells in the late stage of differentiation. Ultrastructural analyses confirmed the presence of ATII-like cells with intracellular composite and lamellar bodies. Finally, induced pluripotent stem cells (iPSCs) were generated from transgenic mice with ATII cell-specific lacZ reporter expression. Again, KGF and DCI synergistically increased SP-C and SP-B expression in iPSC cultures, and lacZ expressing ATII-like cells developed. In conclusion, ATII cell-specific reporter expression enabled the first reliable proof for the generation of murine iPSC-derived ATII cells. In addition, we have shown KGF and DCI to synergistically support the generation of ATII-like cells from ESCs and iPSCs. Combined application of these factors will facilitate more efficient generation of stem cell-derived ATII cells for future basic research and potential therapeutic application.
Publication Title
Keratinocyte growth factor and dexamethasone plus elevated cAMP levels synergistically support pluripotent stem cell differentiation into alveolar epithelial type II cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Caenorhabditis elegans
- 23 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
The plasticity of ageing suggests that longevity may be controlled epigenetically by specific alterations in chromatin state. The link between chromatin and ageing has mostly focused on histone deacetylation by the Sir2 family1, 2, but less is known about the role of other histone modifications in longevity. Histone methylation has a crucial role in development and in maintaining stem cell pluripotency in mammals3. Regulators of histone methylation have been associated with ageing in worms4, 5, 6, 7 and flies8, but characterization of their role and mechanism of action has been limited. Here we identify the ASH-2 trithorax complex9, which trimethylates histone H3 at lysine 4 (H3K4), as a regulator of lifespan in Caenorhabditis elegans in a directed RNA interference (RNAi) screen in fertile worms. Deficiencies in members of the ASH-2 complexASH-2 itself, WDR-5 and the H3K4 methyltransferase SET-2extend worm lifespan. Conversely, the H3K4 demethylase RBR-2 is required for normal lifespan, consistent with the idea that an excess of H3K4 trimethylationa mark associated with active chromatinis detrimental for longevity. Lifespan extension induced by ASH-2 complex deficiency requires the presence of an intact adult germline and the continuous production of mature eggs. ASH-2 and RBR-2 act in the germline, at least in part, to regulate lifespan and to control a set of genes involved in lifespan determination. These results indicate that the longevity of the soma is regulated by an H3K4 methyltransferase/demethylase complex acting in the C. elegans germline.
Publication Title
Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2500
Description
To generate an unbiased view of changes to the retinal gene network in Neurog2 retinal mutants, we generated and compared the P2 transcriptomes from control, heterozygote and mutant mice. A pair of P2 retinas from each biologic replicate were used to produce libraries for high throughput sequencing (n = 5 biologic replicates/genotype). Reads were aligned with BWA and Bowtie programs to the mm10 genome. Aligned reads were then analyzed for differentially expressed transcripts using the CuffDiff program in the Galaxy online bioinformatics package (www.usegalaxy.org). Overall design: Total RNA from Neurog2CKO/CKO(wildtype; n = 5), Chx10Cre;Neurog2CKO/+(heterozygote; n = 5), and Chx10Cre;Neurog2CKO/CKO(mutant; n = 5) P2 retinas.
Publication Title
Requirements for Neurogenin2 during mouse postnatal retinal neurogenesis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 42 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Several clinical trials have shown anti-CD3 treatment to be a promising therapy for autoimmune diabetes, but its mechanism of action remains unclear. Foxp3+ regulatory T (Treg) cells are likely to be involved, and we have shown a strong effect of anti-CD3 on homeostatic control of CD4+ FoxP3+ regulatory T (Treg) cells. To analyze the early consequences of anti-CD3 treatment, we sorted and profiled Treg and conventional CD4+ T (Tconv) cells in the first hours and days after anti-CD3 treatment of NOD mice. In practice, NOD mice carrying the Foxp3-GFP reporter were treated with anti-CD3 mAb KT3 (50 ug iv) and CD4+ T cells were sorted from pooled spleen and lymph nodes after 2, 8, 24 and 72 hrs, separating Treg and Tconv cells on the basis of GFP expression. Anti-CD3 treatment led to a transient transcriptional response, terminating faster than most antigen-induced responses. Most transcripts were similarly induced in Treg and Tconv cells, but several were differential, in particular those encoding the IL7 receptor (IL7R) and transcription factors Id2/3 and Gfi1, upregulated in Treg but repressed in Tconv cells. In parallel experiments, we tested the effect of soluble anti-CD3 added to cultures of fresh splenocytes, sorting Treg and Tconv cells at the same time points. Many of the anti-CD3 elicited changes, and of the differential response observed in vivo, were also observed in vitro. Two independent replicate series; Treg and Tconv samples abbreviated TR and TC, respectively. Keywords: Transcriptional activation, TCR
Publication Title
Differential response of regulatory and conventional CD4⁺ lymphocytes to CD3 engagement: clues to a possible mechanism of anti-CD3 action?
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Affymetrix Hu133 GeneCHIP Microarray data for Control and c-MYC knock-down (KD) human cancer cell lines.
Publication Title
Novel c-MYC target genes mediate differential effects on cell proliferation and migration.
Sample Metadata Fields
No sample metadata fields
View Samples