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GSE469
Mus musculus
66 Downloadable Samples
Affymetrix Murine Genome U74A Array (mgu74a)
Description
Temporal expression profiling was utilized to define transcriptional regulatory pathways in vivo in a mouse muscle regeneration model. Potential downstream targets of MyoD were identified by temporal expression, promoter data base mining, and gel shift assays; Slug and calpain 6 were identified as novel MyoD targets. Slug, a member of the snail/slug family of zinc finger transcriptional repressors critical for mesoderm/ectoderm development, was further shown to be a downstream target by using promoter/reporter constructs and demonstration of defective muscle regeneration in Slug null mice.
Publication Title
Slug is a novel downstream target of MyoD. Temporal profiling in muscle regeneration.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Microarray Analysis of Space-flown Murine Thymus Tissue Reveals Changes in Gene Expression Regulating Stress and Glucocorticoid Receptors. We used microarrays to detail the gene expression of space-flown thymic tissue and identified distinct classes of up-regulated genes during this process. We report here microarray gene expression analysis in young adult C57BL/6NTac mice at 8 weeks of age after exposure to spaceflight aboard the space shuttle (STS-118) for a period of 13 days. Upon conclusion of the mission, thymus lobes were extracted from space flown mice (FLT) as well as age- and sex-matched ground control mice similarly housed in animal enclosure modules (AEM). mRNA was extracted and an automated array analysis for gene expression was performed. Examination of the microarray data revealed 970 individual probes that had a 1.5 fold or greater change. When these data were averaged (n=4), we identified 12 genes that were significantly up- or down-regulated by at least 1.5 fold after spaceflight (p0.05). Together, these data demonstrate that spaceflight induces significant changes in the thymic mRNA expression of genes that regulate stress, glucocorticoid receptor metabolism, and T cell signaling activity. These data explain, in part, the reported systemic compromise of the immune system after exposure to the microgravity of space.
Publication Title
Microarray analysis of spaceflown murine thymus tissue reveals changes in gene expression regulating stress and glucocorticoid receptors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Conditional knockout of Snai1 in the mouse intestinal epithlium results in apoptotic loss of crypt base columnar cells and bias towards differentiation of secretory lineages. In vitro organoid cultures derived from Snail conditional knockout mice also undergo apoptosis when Snai1 is deleted.
Publication Title
Snai1 regulates cell lineage allocation and stem cell maintenance in the mouse intestinal epithelium.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 36 Downloadable Samples
Illumina HiSeq 2000, Illumina HiSeq 3000
Description
Type 1 diabetes is characterized by the destruction of pancreatic beta cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types including glucagon-producing alpha cells. In a genetic model, overexpression of the master regulatory transcription factor Pax4 or loss of its counterplayer Arx are sufficient to induce the conversion of alpha cells to functional beta-like cells. Here we identify artemisinins as small molecules that functionally repress Arx and induce beta-cell characteristics in alpha cells. We show that the protein gephyrin is the mammalian target of these antimalaria drugs. Finally, we demonstrate that gephyrin-mediated enhancement of GABAA receptor signaling is the mechanism of action of these molecules in pancreatic transdifferentiation. Our results indicate that gephyrin is a novel druggable target for the regeneration of pancreatic beta cell mass from alpha cells. Overall design: Transcriptional dissection of Artemether treated, human pancreatic islets of one donor using single-cell RNA-seq
Publication Title
Artemisinins Target GABA<sub>A</sub> Receptor Signaling and Impair α Cell Identity.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Illumina HiSeq 2000
Description
Type 1 diabetes is characterized by the destruction of pancrea tic beta cells, and generating new insulin-producing cells from other cell types is a major aim of regenerative medicine. One promising approach is transdifferentiation of developmentally related pancreatic cell types including glucagon-producing alpha cells. In a genetic model, loss of the master regulatory transcription factor Arx is sufficient to induce the conversion of alpha cells to functional beta-like cells. Here we identify artemisinins as small molecules that functionally repress Arx by causing its translocation to the cytoplasm. We show that the protein gephyrin is the mammalian target of these antimalaria drugs, and that enhancement of GABAA receptor signaling contributes to the mechanism of action of these molecules in pancreatic transdifferentiation. Our results in zebrafish, rodents and primary human pancreatic islets indicate that gephyrin is a novel druggable target for the regeneration of pancreatic beta cell mass from alpha cells. Overall design: There are two parts in the transcriptional study on mouse cell lines in this project. One part is on Min6-ARX inducible cells with different induction time of Dox. This is done in three different clones. The other part is on alpha-TC1 cells. This is done in one concentration of Artemether, one time point and two biological repeats.
Publication Title
Artemisinins Target GABA<sub>A</sub> Receptor Signaling and Impair α Cell Identity.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Previous studies in our laboratory demonstrated that the azurophil granule protease neutrophil elastase (NE) cleaves PML-RARA (PR), the fusion protein that initiates acute promyelocytic leukemia (APL). Further, NE deficiency reduces the penetrance of APL in a murine model of this disease. We therefore predicted that NE-mediated PR cleavage might be important for its ability to initiate APL. To test this hypothesis, we generated a mouse expressing NE-resistant PR. These mice developed APL indistinguishable from wild type PR, but with significantly reduced latency (median leukemia-free survival of 274 days versus 473 days for wild type PR, p<0.001). Resistance to proteolysis may increase the abundance of full length PR protein in early myeloid cells, and our previous data suggested that non-cleaved PR may be less toxic to early myeloid cells. Together, these effects appear to increase the leukemogenicity of NE-resistant PR, contrary to our previous prediction. We conclude that NE deficiency may reduce APL penetrance via indirect mechanisms that are still NE dependent.
Publication Title
A protease-resistant PML-RAR{alpha} has increased leukemogenic potential in a murine model of acute promyelocytic leukemia.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- NextSeq 500
Description
This analysis represents the first comprehensive sampling of germ cells in the developing testis over time, at high-resolution, single-cell depth. From these analyses, we have not only revealed novel genetic regulatory signatures of murine germ cells over time, but have also demonstrated that cell types positive for a single marker gene have the capacity to change dramatically during testis maturation, and therefore cells of a particular “identity” may differ significantly from postnatal to adult life. Overall design: Single-cell suspensions of mammalian testes ranging from PND6 to adult were processed for single-cell RNAseq (10x Genomics Chromium) and libraries were sequenced on a NextSeq500 (Illumina).
Publication Title
Dynamic transcriptome profiles within spermatogonial and spermatocyte populations during postnatal testis maturation revealed by single-cell sequencing.
Sample Metadata Fields
Age, Disease, Cell line, Subject
View Samples- Homo sapiens
- 127 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The characteristics of immune cells infiltrating pediatric brain tumors is largely unexplored. A better understanding of these characteristics will provide a foundation for development of immunotherapy for pediatric brain tumors.
Publication Title
Characterization of distinct immunophenotypes across pediatric brain tumor types.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 104 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To better understand the pathogenesis of acute promyelocytic leukemia (APL, FAB M3 AML), we identified genes that are expressed differently in APL cells compared to other acute myeloid leukemia subtypes, and to normal promyelocytes. Comparative gene expression analysis of 14 M3, 62 other AML (M0, M1, M2 and M4) and 5 enriched normal promyelocyte samples revealed a signature of 1,121 genes that are specifically dysregulated in M3 samples relative to other AML, and that do not simply represent normal promyelocyte expression (M3-specific signature). We used a novel, high throughput digital platform (Nanostring's nCounter system) to evaluate a subset of the most significantly dysregulated genes in 30 AML samples; 33 of 37 evaluable gene expression patterns were validated. In an additional analysis, we selected only genes that are dysregulated in M3 both compared to other AML subtypes, and to purified normal CD34+ cells, promyelocytes, and/or neutrophils, thereby isolating a 478 gene "composite M3 dysregulome". Surprisingly, the expression of only a few of these genes was significantly altered in PR-9 cells after PML-RARA induction, suggesting that most of these genes are not direct targets of PML-RARA. Comparison of the M3-specific signature to our previously described murine APL dysregulome revealed 33 commonly dysregulated genes, including JUN, EGR1, and TNF. Collectively, these results suggest that PML-RARA initiates a transcriptional cascade which generates a unique downstream expression signature in both primary human and mouse APL cells.
Publication Title
High throughput digital quantification of mRNA abundance in primary human acute myeloid leukemia samples.
Sample Metadata Fields
Sex, Race
View Samples- Bos taurus
- 88 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Establishment of an in vitro system to explore molecular mechanisms of mastitis susceptibility in cattle by comparative expression profiling of Escherichia coli and Staphylococcus aureus inoculated primary cells sampled from cows with different genetic predisposition for somatic cell score
Publication Title
Comparative expression profiling of E. coli and S. aureus inoculated primary mammary gland cells sampled from cows with different genetic predispositions for somatic cell score.
Sample Metadata Fields
Disease, Treatment, Time
View Samples