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GSE50617
Mus musculus
10 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Kruppel-like factors are a subclass of zinc finger transcription factors that play important roles in different aspects of cell growth, development, and differentiation. Our group have identified KLF13 as an essential transcription factor for the late expression of chemokine RANTES in T lymphocytes. However, very little is known about the role of KLF13 in T cells and other potential transcriptional targets. To address this, we sought to identify genes that are regulated by KLF13 in mouse T cells. Using microarray analysis, we compared gene expression in activated CD3+ T lymphocytes from wild type and Klf13-/- animals.
Publication Title
KLF13 cooperates with c-Maf to regulate IL-4 expression in CD4+ T cells.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Memory-like T cells are a subset of thymic cells that acquire effector function through the maturation process rather than interaction with specific antigen. Disruption of genes encoding T cell signaling proteins or transcription factors have provided insights into the differentiation of such cells. We show here that in BALB/c but not C57BL/6 mice, a large portion of thymic CD4-CD8+ T cells exhibit a memory-like phenotype. In BALB/c mice, IL-4 secreted by invariant natural killer T (iNKT) cells is both essential and sufficient for the generation of memory-like T cells. In C57BL/6 mice, iNKT cells are less abundant, producing IL-4 that is insufficient to induce thymic memory-like CD8+ T cells. BALB/c mice deficient in the transcription factor Kruppel-like factor (KLF) 13 have comparable numbers of iNKT cells to C57BL/6 mice and extremely low levels of thymic memory-like CD8+ T cells. This work documents the dramatic impact of a small number of KLF13-dependent iNKT cells.
Publication Title
KLF13 sustains thymic memory-like CD8(+) T cells in BALB/c mice by regulating IL-4-generating invariant natural killer T cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Despite advances in contemporary chemotherapeutic strategies, long term survival still remains elusive for patients with metastatic colorectal cancer. A better understanding of the molecular markers of drug sensitivity to match therapy with patient is needed to improve clinical outcomes. In this study, we used in vitro drug sensitivity data from the NCI-60 cell lines together with their Affymetrix microarray data to develop a gene expression signature to predict sensitivity to oxaliplatin. In order to validate our oxaliplatin sensitivity signature, Patient-Derived Colorectal Cancer Explants (PDCCEs) were developed in NOD-SCID mice from resected human colorectal tumors. Analysis of gene expression profiles found similarities between the PDCCEs and their parental human tumors, suggesting their utility to study drug sensitivity in vivo. The oxaliplatin sensitivity signature was then validated in vivo with response data from 14 PDCCEs treated with oxaliplatin and was found to have an accuracy of 92.9% (Sensitivity=87.5%; Specificity=100%). Our findings suggest that PDCCEs can be a novel source to study drug sensitivity in colorectal cancer. Furthermore, genomic-based analysis has the potential to be incorporated into future strategies to optimize individual therapy for patients with metastatic colorectal cancer.
Publication Title
Characterization of an oxaliplatin sensitivity predictor in a preclinical murine model of colorectal cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 47 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Although a number of animal model studies have addressed changes in gene expression in the parenchyma and their relationship to emphysema, much less is known about the pathogenesis of cigarette smoke-induced small airway remodeling. In this study, we exposed rat tracheal explants to whole smoke for 15 minutes, and then cultured the explants in air. The airway transcriptome was evaluated using RAE 230_2 GeneChips. By 2 hours after starting smoke exposure, expression levels of 502 genes were changed up or down by more than 1.5 times (p values <0.01 or less), and by 24 hours, 1870 genes were significantly changed up or down. These included genes involved in anti-oxidant protection, epithelial defense and remodeling, inflammatory mediators and transcription factors, and a number of unexpected genes including the MMP-12 inducer, tachykinin-1 (substance P). Pre-treatment of the explants with 1 x 10-7 M dexamethasone reduced the number of significantly changed genes by approximately 47% at 2 hr and 68% at 24 hours, and in almost all instances, reduced the magnitude of the smoke-induced changes. We conclude that even a very brief exposure to cigarette smoke can lead to rapid changes in the expression of a large number of genes in rat tracheal explants, and that these effects are directly mediated by smoke, without a need for exogenous inflammatory cells. Steroids, contrary to the usual belief, are able to ameliorate many of these changes, at least in this very acute model.
Publication Title
Modification of the rat airway explant transcriptome by cigarette smoke.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 60 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The response to growth hormone in humans is dependent on phenotypic, genetic and environmental factors. The present study in children with growth hormone deficiency (GHD) collected worldwide characterised gene-environment interactions on growth response to recombinant human growth hormone (r-hGH). Growth responses in children are linked to latitude, and we found that a correlation of latitude, summer daylight exposure (SDE) was a key environmental factor related to growth response to r-hGH. In turn growth response was determined by an interaction between both SDE and genes known to affect growth response to r-hGH. In addition analysis of associated networks of gene expression implicated a role for circadian clock pathways and specifically the developmental transcription factor NANOG. This work provides the first observation of gene-environment interactions in children treated with r-hGH.
Publication Title
Effect of summer daylight exposure and genetic background on growth in growth hormone-deficient children.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 2 Downloadable Samples
Description
Organoid technologies provide an accessible system in which to examine the generation, self-organization,and 3-dimensional cellular interactions during development of the human cerebral cortex. However, oligodendrocytes, the myelinating glia of the central nervous system and third major neural cell type, are conspicuously absent from current protocols. Here we reproducibly generate human oligodendrocytes and myelin in pluripotent stem cell-derived cortical spheroids. Transcriptional and immunohistochemical analysis of the spheroids demonstrates molecular features consistent with maturing human oligodendrocytes within 14 weeks of culture, including expression of MyRF, PLP1, and MBP proteins. Histological analysis by electron microscopy shows initial wrapping of human neuronal axons with myelin by 20 weeks and maturation to compact myelin by 30 weeks in culture. Treatment of spheroids with previously identified promyelinating drugs enhances the rate and extent of human oligodendrocyte generation and myelination. Furthermore, generation of spheroids from patients with a severe genetic myelin disorder, Pelizaeus-Merzbacher disease, demonstrates the ability to recapitulate human disease phenotypes, which were in turn improved with both pharmacologic and CRISPR-based approaches. Collectively, these 3-dimensional, multi-lineage cortical spheroids provide a versatile platform to observe and perturb the complex cellular interactions that occur during developmental myelination of the brain and offer new opportunities for disease modeling and therapeutic development in human tissue. Overall design: RNAseq profiles comparing neuro-cortical spheroids and oligo-cortical spheroids
Publication Title
Induction of myelinating oligodendrocytes in human cortical spheroids.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 10 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
The study is relevant to an understanding of the forces that lead to sex differences in the brain and other somatic tissues. Many neural and psychiatric diseases affect men and women differently, so the understanding of sex differences in brain function impacts on our understanding of why the male and female brain differ in their susceptibility to disease.
Publication Title
Sex bias and dosage compensation in the zebra finch versus chicken genomes: general and specialized patterns among birds.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 10 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
The study is relevant to an understanding of the forces that lead to sex differences in the brain. Many neural and psychiatric diseases affect men and women differently, so the understanding of sex differences in brain function impacts on our understanding of why the male and female brain differ in their susceptibility to disease.
Publication Title
Sex bias and dosage compensation in the zebra finch versus chicken genomes: general and specialized patterns among birds.
Sample Metadata Fields
No sample metadata fields
View Samples- Gallus gallus
- 9 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
The study is relevant to an understanding of the forces that lead to sex differences in the brain. Many neural and psychiatric diseases affect men and women differently, so the understanding of sex differences in brain function impacts on our understanding of why the male and female brain differ in their susceptibility to disease.
Publication Title
Sex bias and dosage compensation in the zebra finch versus chicken genomes: general and specialized patterns among birds.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Increasing evidence suggests that Long non-coding RNAs (LncRNAs) represent a new class of regulators of stem cells. However, the roles of LncRNAs in stem cell maintenance and myogenesis remain largely unexamined. For this study, hundreds of novel intergenic LncRNAs were identified that are expressed in myoblasts and regulated during differentiation. One of these LncRNAs, termed LncMyoD, is encoded next to the Myod gene and is directly activated by MyoD during myoblast differentiation. Knockdown of LncMyoD strongly inhibits terminal muscle differentiation largely due to a failure to exit the cell cycle. LncMyoD directly binds to IGF2-mRNA-binding-protein 2 (IMP2) and negatively regulates IMP2-mediated translation of proliferation genes such as N-Ras and c-Myc. While the RNA sequence of LncMyoD is not well-conserved between human and mouse, its locus, gene structure and function is preserved. The MyoD-LncMyoD-IMP2 pathway elucidates a mechanism as to how MyoD blocks proliferation to create a permissive state for differentiation.
Publication Title
A long non-coding RNA, LncMyoD, regulates skeletal muscle differentiation by blocking IMP2-mediated mRNA translation.
Sample Metadata Fields
Age
View Samples