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Drosophila melanogaster
16 Downloadable Samples
Illumina HiSeq 2500, Illumina HiSeq 2000
Description
Drosophila melanogaster neural stem cells (neuroblasts [NBs]) divide asymmetrically by differentially segregating protein determinants into their daughter cells. Although the machinery for asymmetric protein segregation is well understood, the events that reprogram one of the two daughter cells toward terminal differentiation are less clear. In this study, we use time-resolved transcriptional profiling to identify the earliest transcriptional differences between the daughter cells on their way toward distinct fates. By screening for coregulated protein complexes, we identify vacuolar-type H+–ATPase (v-ATPase) among the first and most significantly down-regulated complexes in differentiating daughter cells. We show that v-ATPase is essential for NB growth and persistent activity of the Notch signaling pathway. Our data suggest that v-ATPase and Notch form a regulatory loop that acts in multiple stem cell lineages both during nervous system development and in the adult gut. We provide a unique resource for investigating neural stem cell biology and demonstrate that cell fate changes can be induced by transcriptional regulation of basic, cell-essential pathways. Overall design: Comparison of transcriptomes of wild-type type I NBs and GMCs of different ages (1.5h, 3h or 5h old) isolated by FACS from Drosophila melanogaster larval brains.
Publication Title
Time-resolved transcriptomics in neural stem cells identifies a v-ATPase/Notch regulatory loop.
Sample Metadata Fields
Specimen part, Subject
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
The TRIM-NHL protein Brain tumor (Brat) acts as a tumor suppressor in the Drosophila brain, but how it suppresses tumor formation is not completely understood. Here, we combine temperature controlled brat RNAi with transcriptome analysis to identify the immediate brat targets in Drosophila neuroblasts. Besides the known target Deadpan (Dpn), our experiments identify the transcription factor Zelda (Zld) as a critical target of brat. Our data show that Zld is expressed in neuroblasts and required to allow re-expression of Dpn in transit amplifying intermediate neural progenitors. Upon neuroblast division, Brat is enriched in one daughter cell where its NHL domain directly binds to specific motifs in the 3'UTR of dpn and zld mRNA to mediate their degradation. In brat mutants, both Dpn and Zld continue to be expressed, but inhibition of either transcription factor prevents tumorigenesis. Our genetic and biochemical data indicate that Dpn inhibition requires higher Brat levels than Zld inhibition and suggest a model where stepwise post-transcriptional inhibition of distinct factors ensures sequential generation of fates in a stem cell lineage. Overall design: Comparison of transcriptomes of Drosophila melanogaster control and brat RNAi larval brain type II neural stem cell lineages.
Publication Title
The tumor suppressor Brat controls neuronal stem cell lineages by inhibiting Deadpan and Zelda.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 34 Downloadable Samples
- Illumina HiSeq 2500
Description
Introduction of brain tumor-relevant genetic aberrations initiates different subtypes of brain tumor-like neoplasms in cerebral organoids Overall design: Comparison of abundances (TPM) from different brain tumor organoid groups
Publication Title
Author Correction: Genetically engineered cerebral organoids model brain tumor formation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HiSeq 2500
Description
Introduction of brain tumor-relevant genetic aberrations initiates different subtypes of brain tumor-like neoplasms in cerebral organoids Overall design: Comparison of transcriptomes from different brain tumor organoid groups
Publication Title
Author Correction: Genetically engineered cerebral organoids model brain tumor formation.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- Illumina HiSeq 2500
Description
Engineered brain organoids (enCORs) exhibit reproducible neural differentiation and forebrain regionalization. Overall design: Comparison of transcriptomes from bioengineered micropatterned enCORs and spheroids at 20 days and 60 days
Publication Title
Guided self-organization and cortical plate formation in human brain organoids.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Uridylation of diverse RNA species represents an emerging theme in post-transcriptional gene regulation. In the microRNA pathway, such modifications regulate small RNA biogenesis and stability in plants, worms and mammals. Here, we report the first uridylyltransferase that acts on small RNAs in Drosophila, which we refer to as Tailor. Tailor is the source for the majority of 3´ end-modifications in microRNAs and predominantly targets precursor-hairpins. Uridylation modulates the characteristic two-nucleotide 3´ overhangs of microRNA hairpins, which regulates processing by Dicer-1 and destabilizes RNA hairpins. Furthermore, Tailor preferentially uridylates mirtron-hairpins, thereby impeding the production of non-canonical microRNAs. Mirtron-selectivity is explained by unique primary sequence specificity of Tailor, selecting RNA substrates ending with a 3´ guanosine, a feature not previously observed for TUTases. In contrast to mirtrons, conserved Drosophila pre-miRNAs are significantly depleted in 3´ guanosine, thereby escaping regulatory uridylation. Our data support the hypothesis that evolutionary adaptation to pre-miRNA uridylation shapes the nucleotide composition of pre-miRNA 3´ ends. Hence, hairpin-uridylation may serve as a barrier for the de novo creation of miRNAs in Drosophila. Overall design: mRNA sequencing of Drosophila S2 cells (3-times; control libraries) and three biological replicates of S2 cells stably depleted of CG1091/Tailor by CRISPR/Cas9
Publication Title
Uridylation of RNA Hairpins by Tailor Confines the Emergence of MicroRNAs in Drosophila.
Sample Metadata Fields
Cell line, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina Genome Analyzer II, Illumina HiSeq 2000
Description
Drosophila neuroblasts have emerged as a model for stem cell biology that is ideal for genetic analysis but is limited by the lack of cell-type specific gene expression data. Here, we describe a methodology to isolate large numbers of pure neuroblasts and differentiating neurons that retain both cell cycle and lineage characteristics. We determine transcriptional profiles by mRNA sequencing and identify 28 predicted neuroblast specific transcription factors, which can be arranged in a network containing hubs for Notch signaling, growth control and chromatin regulation. Overexpression and RNAi for these factors identify Klumpfuss as a regulator of self-renewal. We show that loss of Klu function causes premature differentiation while overexpression results in the formation of transplantable brain tumors. Our data represent a valuable resource for Drosophila developmental neurobiology and we describes methodology that can be applied to other invertebrate stem cell lineages as well. Overall design: comparison of transcriptomes of Drosophila melanogaster larval neuroblasts and their differentiated daughter cells (neurons)
Publication Title
FACS purification and transcriptome analysis of drosophila neural stem cells reveals a role for Klumpfuss in self-renewal.
Sample Metadata Fields
Specimen part, Subject
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SRP131953- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
Human cytotrophoblast organoid cultures were established from the villous trophoblast of first trimester placentas. We analyzed the global expression profile of the cytotrophoblast organoids (CTB-ORG) and compared to the profile of the tissue of origin i.e. villous cytotrophoblast (vCTB) as well as to differentiated syncytiotrophoblast (STB) and placental fibroblasts (FIB). Overall design: We employed QuantSeq method to analyzed the global expression profile of the cytotrophoblast organoids (4 replicates, CTB-ORG 1-4) and compared to the profile of the tissue of origin i.e. villous cytotrophoblast (3 replicates, vCTB 1-3) as well as to in vitro differentiated syncytiotrophoblast (3 replicates, STB1-3) and placental fibroblasts (2 replicates, FIB 1-2).
Publication Title
Self-Renewing Trophoblast Organoids Recapitulate the Developmental Program of the Early Human Placenta.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Increased ploidy is common in tumors but treatments for tumors with excess chromosome sets are not available. Here, we characterize high-ploidy breast cancers and identify potential anticancer compounds selective for the high-ploidy state. Among 354 human breast cancers, 10% have mean chromosome copy number exceeding 3, and this is most common in triple negative and HER2-positive types. Women with high-ploidy breast cancers have higher risk of recurrence and death in two patient cohorts, demonstrating that it represents an important group for improved treatment. Because high-ploidy cancers are aneuploid, rather than triploid or tetraploid, we devised a two-step screen to identify selective compounds. The screen was designed to assure both external validity on diverse karyotypic backgrounds and specificity for high-ploidy cell types. This screen identified novel therapies specific to high-ploidy cells. First, we discovered 8-azaguanine, an antimetabolite that is activated by hypoxanthine phosphoribosyltransferase (HPRT), suggesting an elevated gene-dosage of HPRT in high-ploidy tumors can control sensitivity to this drug. Second, we discovered a novel compound, 2,3-Diphenylbenzo[g]quinoxaline-5,10-dione (DPBQ). DPBQ activates p53 and triggers apoptosis in a polyploid-specific manner, but does not inhibit topoisomerase or bind DNA. Mechanistic analysis demonstrates that DPBQ elicits a hypoxia gene signature and its effect is replicated, in part, by enhancing oxidative stress. Structure-function analysis defines the core benzo[g]quinoxaline-5,10 dione as being necessary for the polyploid-specific effects of DPBQ. We conclude that polyploid breast cancers represent a high-risk subgroup and that DPBQ provides a functional core to develop polyploid-selective therapy.
Publication Title
Identification of Selective Lead Compounds for Treatment of High-Ploidy Breast Cancer.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
This experiment was conducted to identify target genes of the peroxisome proliferator-activated receptor beta (PPARb) in skeletal muscle of transgenic mice that overexpressed PPARb.
Publication Title
The nuclear receptor PPARβ/δ programs muscle glucose metabolism in cooperation with AMPK and MEF2.
Sample Metadata Fields
Age, Specimen part
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