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Drosophila melanogaster
1 Downloadable Sample
Illumina HiSeq 2000
Description
Neuroendocrine (NE) cells use large dense core vesicles (LDCVs) to traffic, process, store and secrete neuropeptide hormones through the regulated secretory pathway. The DIMM basic helix-loop-helix transcription factor of Drosophila controls the level of regulated secretory activity in NE cells. To pursue its mechanisms, we have performed two independent genome-wide analyses of DIMM's activities: (i) in vivo chromatin immunoprecipitation (ChIP) to define genomic sites of DIMM occupancy and (ii) deep sequencing of purified DIMM neurons to characterize their transcriptional profile. By this combined approach, we showed that DIMM binds to conserved E-boxes in enhancers of 212 genes whose expression is enriched in DIMM-expressing NE cells. DIMM binds preferentially to certain E-boxes within first introns of specific gene isoforms. Statistical machine learning revealed that flanking regions of putative DIMM binding sites contribute to its DNA binding specificity. DIMM's transcriptional repertoire features at least 20 LDCV constituents. In addition, DIMM notably targets the pro-secretory transcription factor, CREB-A, but significantly, DIMM does not target any neuropeptide genes. DIMM therefore prescribes the scale of secretory activity in NE neurons, by a systematic control of the regulated secretory pathway at steps that are both proximal and distal.
Publication Title
Genome-wide features of neuroendocrine regulation in Drosophila by the basic helix-loop-helix transcription factor DIMMED.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 402 Downloadable Samples
- IlluminaGenomeAnalyzer
Description
Purpose: The purpose of this study is to identify functionally inter-connected group of miRNAs whose reduced expression promotes leukemia development in vivo. We searched for relevant target genes of these miRNAs that are upregulated in T-ALL relative to controls. Methods: In order to examine the global gene expression, we generated 9 T-ALL patients and 4 normal controls by deep sequencing using Illumina Hi-Seq sequencer. The sequence reads that passed quality filters were analyzed using Spliced Transcripts Alignment to a Reference aligner (STAR) followed by differential gene expression analysis using DESeq. Results: Using an optimized data analysis workflow, we mapped reads per sample to the human genome (build hg19) and identified transcripts in both patient and controls with STAR workflow. We applied a machine learning approach to eliminate targets with redundant miRNA-mediated control. This strategy finds a convergence on the Myb oncogene and less prominent effects on the Hpb1 transcription factor. The abundance of both genes is increased in T-ALL and each can promote T-ALL in vivo. Conclusion: Our study reveals a Myc regulated network of tumor suppressor miRNAs in T-ALL. We identified a small number of functionally validated tumor suppressor miRNAs. These miRNAs are repressed upon Myc activation and this links their expression directly to Myb a key oncogenic driver in T-ALL. Overall design: Examination of global gene expression in 9 T-ALL patients and 4 normal controls using total RNA sequencing. BaseMeanA in DESeq_results.xlsx is the control.
Publication Title
Characterization of a set of tumor suppressor microRNAs in T cell acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
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GSE57944- Homo sapiens
- 7 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma.
Sample Metadata Fields
Age, Specimen part, Disease, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Characterization of intraepithelial ILC on the basis of CD8 and Ly49E expression
Publication Title
A Murine Intestinal Intraepithelial NKp46-Negative Innate Lymphoid Cell Population Characterized by Group 1 Properties.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 7 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hepatosplenic T-cell lymphoma (HSTL) is an aggressive lymphoma cytogenetically characterized by isochromosome 7q [i(7)(q10)], of which the molecular consequences remain unknown. We report here results of an integrative genomic and transcriptomic (expression microarray and RNA-sequencing) study of six HSTL cases with i(7)(q10) and three cases with ring 7 [r(7)], a rare variant aberration. Using high resolution array CGH, we prove that HSTL is characterized by the common loss of a 34.88 Mb region at 7p22.1p14.1 (3506316-38406226 bp) and duplication/amplification of a 38.77 Mb region at 7q22.11q31.1 (86259620-124892276 bp). Our data indicate that i(7)(q10)/r(7)-associated loss of 7p22.1p14.1 is a critical event in the development of HSTL, while gain of 7q sequences drives progression of the disease and underlies its intrinsic chemoresistance. Loss of 7p22.1p14.1 does not target a postulated tumor suppressor gene but unexpectedly enhances the expression of CHN2 from the remaining 7p allele, resulting in overexpression of 2-chimerin and dysregulation of a pathway involving RAC1 and NFATC2 with a cell proliferation response. Gain of 7q leads to increased expression of critical genes, including RUNDC3B, PPP1R9A and ABCB1, a known multidrug resistance gene. RNA-sequencing did not identify any additional recurrent mutations or gene fusions, suggesting that i(7)(q10) is the only driver event in this tumor. Our study confirms the previously described gene expression profile of HSTL and identifies a set of 24 genes, including three located on chromosome 7 (CHN2, ABCB1 and PPP1R9A), distinguishing HSTL from other malignancies
Publication Title
Integrative genomic and transcriptomic analysis identified candidate genes implicated in the pathogenesis of hepatosplenic T-cell lymphoma.
Sample Metadata Fields
Age, Specimen part, Treatment
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Comparison between ex vivo immature, mature and stimulated T cells and in vitro generated counterparts. The T cells generated in vitro were cultured on OP9-DL1 stroma supplied with growth factors.
Publication Title
In vitro generation of mature, naive antigen-specific CD8(+) T cells with a single T-cell receptor by agonist selection.
Sample Metadata Fields
Specimen part
View Samples- Drosophila melanogaster
- 7 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
To amass candidate DIMM targets in addition to Phm (Park et al., 2008a), we used genome-wide microarray profiling by over-expressing DIMM throughout the embryonic nervous system. We compared profiles from experimental (elav>dimm) and control (elav-GAL4) embryos at 22-26 hr and 28-32 hr after egg laying (AEL). The design was intended to identify transcripts consistently up-regulated shortly after the induction of DIMM; in so doing, we could circumvent the lethality that ensues in late embryonic, and/ or by early larval stages, due to pan-neuronal DIMM expression.
Publication Title
Molecular organization of Drosophila neuroendocrine cells by Dimmed.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 57 Downloadable Samples
- NextSeq 500
Description
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive type of blood cancer resulting from malignant transformation of T-cell precursors. Several oncogenes, including the 'T-cell leukemia homeobox 1' TLX1 (HOX11) transcription factor, have been identified as early driver events that cooperate with other genetic aberrations in leukemic transformation of progenitor T-cells. The TLX1 controlled transcriptome in T-ALL has been investigated extensively in the past in terms of protein-coding genes, but remains unexplored thus far at the level of long non-coding RNAs (lncRNAs), the latter renown as well-established versatile and key players implicated in various cancer hallmarks. In this study, we present the first extensive analysis of the TLX1 regulated transcriptome focusing on lncRNA expression patterns. We present an integrative analysis of polyA and total RNA sequencing of ALL-SIL lymphoblasts with perturbed TLX1 expression and a primary T-ALL patient cohort (including 5 TLX1+ and 12 TLX3+ cases). We expanded our initially presented dataset of TLX1 and H3K27ac ChIP data in ALL-SIL cells (Durinck et al., Leukemia, 2015) with H3K4me1, H3K4me3, and ATAC-seq data to accurately define (super-) enhancer marked lncRNAs and assigned potential functional annotations to candidate TLX1-controlled lncRNAs through an in silico guilt-by-association approach. Our study paves the way for further functional analysis of selected lncRNAs as potential novel therapeutic targets for a precision medicine approach in the context of T-ALL. Overall design: polyA+ RNA-seq data was generated for a primary T-ALL patient cohort
Publication Title
A comprehensive inventory of TLX1 controlled long non-coding RNAs in T-cell acute lymphoblastic leukemia through polyA+ and total RNA sequencing.
Sample Metadata Fields
Subject
View Samples GSE27833- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Notch signaling is one of the central regulators of differentiation in a variety of organisms and tissue types. Within the hematopoietic system, Notch is essential for the emergence of definitive HSC during fetal life and controls adult HSC differentiation to the T-cell lineage. Notch activation is controlled by the gamma-secretase complex complex, composed of presenilin, nicastrin (Ncstn), anterior pharynx-1 (Aph1), and presenilin enhancer-2
Publication Title
A novel tumour-suppressor function for the Notch pathway in myeloid leukaemia.
Sample Metadata Fields
Sex, Age
View Samples