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SRP127343
Homo sapiens
72 Downloadable Samples
Illumina HiSeq 4000
Description
Aberrations in genes coding for subunits of the BAF chromatin remodeling complex are highly abundant in human cancers. Currently, it is not understood how these loss-of-function mutations contribute to cancer development and how they can be targeted therapeutically. The cancer type specific occurrence patterns of certain subunit mutations suggest subunit-specific effects on BAF complex function, possibly by the formation of aberrant residual complexes. Here, we systematically characterize the effects of individual subunit loss on complex composition, chromatin accessibility and gene expression in a panel of knock-out cell lines deficient for 22 targetable BAF subunits. We observe strong, specific and often discordant alterations dependent on the targeted subunit and show that these explain intra-complex co-dependencies, including the novel synthetic lethal interactions SMARCA4-ARID2, SMARCA4-ACTB and SMARCC1-SMARCC2. These data provide insights into the role of different BAF subcomplexes in genome-wide chromatin organization and suggest novel approaches to therapeutically target BAF mutant cancers. Overall design: RNA-seq samples for knockouts of BAF complex in the HAP1 cell line.
Publication Title
Systematic characterization of BAF mutations provides insights into intracomplex synthetic lethalities in human cancers.
Sample Metadata Fields
Cell line, Subject
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- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Identification of intrathymic Eomes+ natural Th1 cells creates a novel idea that there is more than one way for the generation of innate CD4 T cells. To more deeply characterize this type of innate T cells, we compared the gene expression profile between nTh1 cells generated in CIITAtg mice and classic Th1 cells differentiated from naive CD4 T cells in Th1-polarizing condition.
Publication Title
Thymic low affinity/avidity interaction selects natural Th1 cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
It is unknown if gene expression profiles from primary RCC tumors differ from patient-matched metastatic tumors. Thus, we sought to identify differentially expressed genes between patient-matched primary and metastatic RCC tumors in order to understand the molecular mechanisms underlying the development of RCC metastases.
Publication Title
Differential gene expression profiling of matched primary renal cell carcinoma and metastases reveals upregulation of extracellular matrix genes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Terahertz (THz) technology has emerged for biomedical applications such as scanning, molecular spectroscopy, and medical imaging. However, the biological effect of THz radiation is not fully understood. Non-thermal effects of THz radiation were investigated by applying a femtosecond-terahertz (fs-THz) pulse to mouse skin. Analysis of the genome-wide expression profile in fs-THz-irradiated skin indicated that wound responses were predominantly through NFB1- and Smad3/4-mediated transcriptional activation. Repeated fs-THz radiation delayed the closure of mouse skin punch wounds due to up-regulation of transforming growth factor-beta (TGF-). These findings suggest that fs-THz radiation provokes a wound-like signal in skin with increased expression of TGF- and activation of its downstream target genes, which perturbs the wound healing process in vivo.
Publication Title
High-power femtosecond-terahertz pulse induces a wound response in mouse skin.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
We report the ability of the Drosha null/conditional-null mouse model to enable the identification of pri-miRNA transcripts. The conditional-null allele of Drosha phenocopies the null allele both in mESC and in mice, upon conversion to the null state with Cre. Overall design: Examination of the effects of Drosha deficiency in mouse embryonic stem cells.
Publication Title
microTSS: accurate microRNA transcription start site identification reveals a significant number of divergent pri-miRNAs.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The overall goal of this project is to investigate the role of Erk2-mediated signaling in regulating the cellular metabolism of cranial neural crest (CNC) cells during palate development. Here, we conducted gene expression profiling of palate tissue from wild type mice as well as those with a neural crest specific conditional inactivation of the Erk2 gene. The latter mice exhibit micrognathia, tongue defects and cleft palate, which is among the most common congenital birth defects and observed in many syndromic conditions.
Publication Title
Disruption of the ERK/MAPK pathway in neural crest cells as a potential cause of Pierre Robin sequence.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 71 Downloadable Samples
- IlluminaHiSeq2500
Description
We discovered induction of circular RNA in human fetal tissues, including the heart. In this study, we were able to recapitulate this induction by in vitro directed differentiation of hESCs to cardiomyocytes, paving the way for future studies into circular RNA regulation. Overall design: We harvested hESCs at sequential stages of differentiation: undifferentiated (day 0), mesoderm (day 2), cardiac progenitor (day 5) and definitive cardiomyocyte (day 14). We performed RNA sequencing in biological triplicate, with 3-8 technical replicates each.
Publication Title
Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 35 Downloadable Samples
- IlluminaHiSeq2000
Description
The pervasive expression of circular RNA from protein coding loci is a recently discovered feature of many eukaryotic gene expression programs. Computational methods to discover and quantify circular RNA are essential to the study of the mechanisms of circular RNA biogenesis and potential functional roles they may play. In this paper, we present a new statistical algorithm that increases the sensitivity and specificity of circular RNA detection.by discovering and quantifying circular and linear RNA splicing events at both annotated exon boundaries and in un-annotated regions of the genome Unlike previous approaches which rely on heuristics like read count and homology between exons predicted to be circularized to determine confidence in prediction of circular RNA expression, our algorithm is a statistical approach. We have used this algorithm to discover general induction of circular RNAs in many tissues during human fetal development. We find that some regions of the brain show marked enrichment for genes where circular RNA is the dominant isoform. Beyond this global trend, specific circular RNAs are tissue specifically induced during fetal development, including a circular isoform of NCX1 in the developing fetal heart that, by 20 weeks, is more highly expressed than the linear isoform as well as beta-actin. In addition, while the vast majority of circular RNA production occurs at canonical U2 (major spliceosome) splice sites, we find the first examples of developmentally induced circular RNAs processed by the U12 (minor) spliceosome, and an enriched propensity of U12 donors to splice into circular RNA at un-annotated, rather than annotated, exons. Together, our algorithm and its results suggest a potentially significant role for circular RNA in human development. Overall design: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA with Ribo-Zero Gold sample prep kit.
Publication Title
Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development.
Sample Metadata Fields
No sample metadata fields
View Samples