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SRP079357
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
- 374 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Obesity has considerable effects on morbidity and mortality, and the prevalence of obesity has been increasing rapidly worldwide during the past two decades. Even if obesity affects the entire individual, adipose tissue plays a central role in the development of obesity. Expression profiling of adipose tissue may give insights into the mechanisms contributing to obesity and obesity-related disorders.
Publication Title
Adipose tissue resting energy expenditure and expression of genes involved in mitochondrial function are higher in women than in men.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Obesity has considerable effects on morbidity and mortality and the prevalence of obesity has been increasing rapidly worldwide during the past two decades. Even if obesity affects the entire individual, adipose tissue play a central role in the development of obesity. Expression profiling of adipose tissue may give insights into mechanisms contributing to obesity and obesity-related disorders.
Publication Title
Adipose tissue resting energy expenditure and expression of genes involved in mitochondrial function are higher in women than in men.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Analysis of rapamycin effects on white adipose tissue at gene expression level. The hypothesis tested in the present study was that rapamycin could modify immune cell composition and inflammatory state of the adipose tissue of obese mice.
Publication Title
Beneficial metabolic effects of rapamycin are associated with enhanced regulatory cells in diet-induced obese mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 121 Downloadable Samples
- NextSeq 500
Description
We used mammosphere formation assay and label-retention assay as functional cellular approaches to enrich for cells with different degree of cancer stem cell properties in the breast cancer cell line MDA-MB-231 and performed single-cell RNA sequencing Overall design: Single cells from three different populations: 30 cells from G1 cell cycle phase cultured in adherent conditions, 46 cells with low proliferation cultured in non-adherent conditions (mammosphere assasy), 45 cells with high proliferation cultured in non-adherent conditions (mammosphere assay)
Publication Title
Erratum: Identification of Breast Cancer Stem Cell Related Genes Using Functional Cellular Assays Combined With Single-Cell RNA Sequencing in MDA-MB-231 Cells.
Sample Metadata Fields
Cell line, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
The importance of the role of microRNAs in gene expression and disease is well recognized. However, what is less appreciated is that almost half of miRNA genes are organized in polycistronic clusters and are therefore co-expressed. The mir-11~998 cluster consists of two miRNAs, miR-11 and miR-998. Here, we describe a novel layer of regulation that links the processing and expression of miR-998 to the presence of the mir-11 gene. We show that the presence of mir-11 in the pri-miRNA is required for processing by Drosha, and deletion of mir-11 prevents the expression of miR-998. Replacing mir-11 with an unrelated miRNA rescued miR-998 expression in vivo and in vitro, as did expressing miR-998 from a shorter, more canonical miRNA scaffold. The embedded regulation of miR-998 is functionally important because unchecked miR-998 expression in the absence of miR-11 resulted in highly penetrant pleiotropic developmental defects. We further show that this novel regulation of expression of miRNAs within a cluster is not limited to the mir-11~998 cluster and likely reflects the more general cis-regulation of expression of individual miRNAs. Thus, our results reveal a novel layer of regulation within miRNA clusters that tempers the functions of the individual miRNAs. Unlinking their expression has the potential to change the expression of multiple miRNA targets and shift biological response. Overall design: RNA was extracted from Drosophila third instar larval eye discs of animals grown in standard conditions; Illumina HiSeq2000 Next Gen RNA Sequencing was performed, and differential expression of genes was assessed in wild-type vs unchecked miR-998 expression
Publication Title
Novel regulation and functional interaction of polycistronic miRNAs.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Expression of dE2F1 induces proliferation and apoptosis. We sought to perform an unbiased analysis of the effect of co-expression of miR-11
Publication Title
mir-11 limits the proapoptotic function of its host gene, dE2f1.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 12 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Third instar larval eye discs provide an in vivo model for cell cycle exit studies. Posterior to the Second Mitotic Wave proliferation is absent in a wild type eye disc. Inactivating mutations in tumor suppressor-like genes can lead to genome wide changes in gene expression that allow for inappropriate bypass of cell cycle exit signals posterior to the Second Mitotic Wave.
Publication Title
Cooperation between dE2F1 and Yki/Sd defines a distinct transcriptional program necessary to bypass cell cycle exit.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We used microarrays to identify genes that are differentially expressed in the absence of miR-998 expression.
Publication Title
An intronic microRNA links Rb/E2F and EGFR signaling.
Sample Metadata Fields
Specimen part
View Samples