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GSE61284
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Engagement of the ICOS receptor represents a key event in a process that culminates in Bcl6 expression and acquisition of the TFH and TFR phenotype. To better understand the essentials of ICOS-mediated signaling pathway, we profiled the changes in gene expression elicited after co-ligation of ICOS and CD3 compared with CD3 ligation alone.
Publication Title
A p85α-osteopontin axis couples the receptor ICOS to sustained Bcl-6 expression by follicular helper and regulatory T cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
NextSeq 500
Description
This study aimed to explore the role of NIPP1 in adult germline cell proliferation and differentiation, using a ubiquitous inducible NIPP1 knockout (TKO) mouse model. To gain unbiased insight into the molecular mechanism that underly the sertoli-only phenotype in TKO, we performed a comparative RNA sequencing profiling of control and TKO, in which NIPP1 was tamoxifin-induced depleted. Overall design: Two genotypes are compared after treatment with tamoxifen. The control genotype (UBC CRE-ERT2+/- Ppp1r8 fl/+) looses the floxed allele of PPP1R8 (aka NIPP1) as a consequence of the treatment with tamoxifen and becomes heterozygous for PPP1R8. The KO genotype (UBC CRE-ERT2+/- Ppp1r8 fl/-) also looses the floxed allele of PPP1R8 as a consequence of the tamoxifen treatment and becomes homozygous KO. For each genotype, 4 replicates are profiled.
Publication Title
The protein phosphatase 1 regulator NIPP1 is essential for mammalian spermatogenesis.
Sample Metadata Fields
Age, Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Somatic ribosomal protein defects have recently been described in cancer, yet their impact on cellular transcription and translation remain poorly understood. Here we integrated mRNA sequencing, ribosome footprinting, polysomal RNA seq and quantitative mass spectrometry datasets obtained from an isogenic mouse lymphoid cell model in order to study the T-cell acute lymphoblastic leukemia (T-ALL) associated R98S mutation in ribosomal protein L10 (RPL10 R98S). RPL10 R98S induced changes in protein levels were to a much larger extent caused by transcriptional then translational changes and RPL10 R98S cells showed a gene signature corresponding to deregulation of hematopoietic transcription factors. Phosphoserine phosphatase (PSPH), a key enzyme in serine biosynthesis, displayed elevated transcription and translation and was one of the proteins showing the strongest upregulation in RPL10 R98S cells. Increased Psph protein levels were confirmed in RPL10 R98S engineered JURKAT cells and in hematopoietic cell cultures derived from Rpl10 R98S knock-in mice. Moreover, elevated serine and glycine biosynthesis in RPL10 R98S cells was supported by metabolic flux analyses. Analysis of PSPH expression levels in T-ALL patient samples revealed that PSPH upregulation is a generalized phenomenon in this disease, associated with elevated circulating serine and glycine levels. Addition of serine and glycine enhanced survival of stromal and myeloid cells, suggesting supportive effects on the hematopoietic niche. Finally, reduction of PSPH expression levels in T-ALL cell lines suppressed their in vitro proliferation and their capacity to expand in T-ALL xenograft models. In conclusion, transcriptome, translatome and proteome analysis of the RPL10 R98S mutation identified RPL10 R98S driven induction of cellular serine biosynthesis. Whereas serine metabolism has been implicated in cancer via PHGDH amplification, this is the first report supporting dependence of ALL cells on the serine biosynthesis enzyme PSPH. Overall design: 3 biological replicates for each condition (RPL10 R98S, RPL10 WT)
Publication Title
Translatome analysis reveals altered serine and glycine metabolism in T-cell acute lymphoblastic leukemia cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 114 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
In this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery
Publication Title
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
In this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery
Publication Title
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
In this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery
Publication Title
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We carried out a global survey of age-related changes in mRNA levels in the C57BL/6NIA mouse hippocampus and found a difference in the hippocampal gene expression profile between 2-month-old young mice and 15-month-old middle-aged mice correlated with an age-related cognitive deficit in hippocampal-based explicit memory formation. Middle-aged mice displayed a mild but specific deficit in spatial memory in the Morris water maze.
Publication Title
Altered hippocampal transcript profile accompanies an age-related spatial memory deficit in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Danio rerio
- 12 Downloadable Samples
- IlluminaHiSeq2000
Description
Macrophage expressed gene 1 (MPEG1) encodes an evolutionary conserved protein with a predicted Membrane Attack Complex/Perforin domain associated with host defence against invading pathogens. In vertebrates, MPEG1 is an integral membrane protein of macrophages, but how it contributes to the macrophage defence mechanisms remains unknown. Zebrafish have three copies of MPEG1, two of which (mpeg1 and mpeg1.2) are expressed in macrophages whereas the third could be a pseudogene. The mpeg1 and mpeg1.2 genes show differential regulation during infection of zebrafish embryos with the bacterial pathogens, Mycobacterium marinum and Salmonella typhimurium. While mpeg1 is down-regulated during infection with both pathogens, mpeg1.2 is infection inducible. Up-regulation of mpeg1.2 is partially dependent on the presence of functional Mpeg1, and requires the Toll-like receptor adaptor molecule MyD88 and transcription factor NF?B. Knockdown of mpeg1 alters the immune response to M. marinum infection and results in increased bacterial burden. In S. typhimurium infection, both mpeg1 and mpeg1.2 knockdown increase bacterial burdens, but mpeg1 morphants show an increased survival rate. The combined results of these two in vivo infection models support the anti-bacterial function of the Mpeg1 family and indicate that the intricate cross-regulation of the two mpeg1 copies aids the zebrafish host in combatting infection Overall design: Embryos were injected at the one cell stage with a morpholino targeting mpeg1, or with the standard control morpholino from GeneTools, or with a morpholino targeting ptpn6 (Kanwal et al., 2013, J. Immunol 190:1631-45) for comparison. Subsequently, at 24 hours post fertilisation (hpf) the morphants and their controls were manually dechorionated at 24 hpf and at 28 hpf they were infected by injecting 200 colony forming units of M. marinum Mma20 into the caudal vein, or mock-injected with PBS/2%PVP. After injections embryos were transferred into fresh egg water containing 0.003% 1-phenyl-2-thiourea (Sigma-Aldrich) to prevent melanisation and incubated for 4 days at 28°C. After the incubation period, infected and uninfected morphants, mutants and their controls were imaged and groups of 30 embryos were snap-frozen in liquid nitrogen and RNA was isolated for Illumina RNAseq analysis.
Publication Title
Macrophage-expressed perforins mpeg1 and mpeg1.2 have an anti-bacterial function in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 11 Downloadable Samples
- IlluminaHiSeq2000
Description
MyD88 is an adaptor protein in Toll-like receptor and interleukin 1 receptor mediated signaling pathways that plays an essential role in activation of immune responses following pathogen recognition. We investigate that role in the zebrafish embryo model by using a zebrafish mutant line that contains a premature stop condon in the gene encoding MyD88, leading to a truncated protein that lacks domains important for its normal function. We infected these MyD88 mutants and wildtype individuals with Mycobacterium marinum to compare the resulting immune response by transcriptome profiling on total RNA isolated from single embryos. Autophagy regulator dram1 was identified as one of the MyD88-dependent genes. Overall design: This RNAseq analysis was used to determine the effect of a truncation of the MyD88 protein on the innate immune response of zebrafish embryos during infection with Mycobacterium marinum. Myd88 mutant and wild type embryos were derived by incrossing homozygous myd88 mutant parents (allele hu3568, van der Vaart et al., 2013, Disease models & mechanisms 6, 841-854) or their wildtype siblings. RNA was isolated from pools of 20 embryos at 4 days post infection (4 dpi). The following treatment groups were used: homozygous mutants mock-injected with PBS/2%PVP 4 dpi, (2) wildtype siblings mock-injected with PBS/2%PVP 4dpi, (3) M. marinum-infected homozygous mutants 4dpi, (4) M. marinum-infected wildtype siblings 4dpi. Embryos were grown at 28.5–30°C in egg water and manually dechorionated at 24 hours post fertilization (hpf). Subsequently, embryos were infected at 28 hpf by micro-injecting 200 colony forming units (CFU) of Mycobacterium marinum Mma20 bacteria into the caudal vein, or were mock-injected with buffer (PBS/2%PVP) as a control. After injections embryos were transferred into fresh egg water and incubated for 4 days at 28°C. After the incubation period, single embryos were snap-frozen in liquid nitrogen and RNA was isolated for RNAseq analysis.
Publication Title
Macrophage-expressed perforins mpeg1 and mpeg1.2 have an anti-bacterial function in zebrafish.
Sample Metadata Fields
No sample metadata fields
View Samples