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GSE20097
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
MicroRNAs (miRNAs) have emerged as novel cancer genes. In particular, the 17~92 cluster of miRNAs is highly expressed in haematopoietic cancers and promotes lymphomagenesis in vivo1,2. Clinical use of these findings hinges on isolating the oncogenic activity within the 17~92 cluster and defining its relevant target genes. Here we show that miR-19 is sufficient to promote leukaemogenesis in Notch1 induced T-cell lymphoblastic leukaemia (T-ALL) in vivo. Consistent with the pathogenic importance of this interaction, we report a novel translocation targeting the 17~92 miRNA cluster coinciding with a second rearrangement that activates Notch1 in T-ALL. To identify the miR-19 targets responsible for its oncogenic action, we conducted a large-scale short-hairpin RNA (shRNA) screen for genes whose knockdown could phenocopy miR-19. Strikingly, the results of this screen were enriched for miR-19 target genes, and included Bim (Bcl2L11)1,3, AMP-activated kinase (Prkaa1), and the tumour suppressor phosphatases Pten and PP2A (Ppp2r5e). Hence, an unbiased, functional genomics approach reveals a coordinate clamp down on several regulators of PI3K-related survival signals by the leukaemogenic miR-19.
Publication Title
Genome-wide RNA-mediated interference screen identifies miR-19 targets in Notch-induced T-cell acute lymphoblastic leukaemia.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Somatic ribosomal protein defects have recently been described in cancer, yet their impact on cellular transcription and translation remain poorly understood. Here we integrated mRNA sequencing, ribosome footprinting, polysomal RNA seq and quantitative mass spectrometry datasets obtained from an isogenic mouse lymphoid cell model in order to study the T-cell acute lymphoblastic leukemia (T-ALL) associated R98S mutation in ribosomal protein L10 (RPL10 R98S). RPL10 R98S induced changes in protein levels were to a much larger extent caused by transcriptional then translational changes and RPL10 R98S cells showed a gene signature corresponding to deregulation of hematopoietic transcription factors. Phosphoserine phosphatase (PSPH), a key enzyme in serine biosynthesis, displayed elevated transcription and translation and was one of the proteins showing the strongest upregulation in RPL10 R98S cells. Increased Psph protein levels were confirmed in RPL10 R98S engineered JURKAT cells and in hematopoietic cell cultures derived from Rpl10 R98S knock-in mice. Moreover, elevated serine and glycine biosynthesis in RPL10 R98S cells was supported by metabolic flux analyses. Analysis of PSPH expression levels in T-ALL patient samples revealed that PSPH upregulation is a generalized phenomenon in this disease, associated with elevated circulating serine and glycine levels. Addition of serine and glycine enhanced survival of stromal and myeloid cells, suggesting supportive effects on the hematopoietic niche. Finally, reduction of PSPH expression levels in T-ALL cell lines suppressed their in vitro proliferation and their capacity to expand in T-ALL xenograft models. In conclusion, transcriptome, translatome and proteome analysis of the RPL10 R98S mutation identified RPL10 R98S driven induction of cellular serine biosynthesis. Whereas serine metabolism has been implicated in cancer via PHGDH amplification, this is the first report supporting dependence of ALL cells on the serine biosynthesis enzyme PSPH. Overall design: 3 biological replicates for each condition (RPL10 R98S, RPL10 WT)
Publication Title
Translatome analysis reveals altered serine and glycine metabolism in T-cell acute lymphoblastic leukemia cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
T-cell acute lymphoblastic leukemia (T-ALL) is an immature hematopoietic malignancy driven mainly by oncogenic activation of NOTCH1 signaling. In this study we used a mouse model of T-ALL through the overexpression of the intarcellular transcriptionally active part of Notch1 (N1-IC). This model faithfully recapitulates the major characteristics of the human disease. Comparison of the leukemic cells from peripheral tumors(thymoma) of this mouse model to normal thymic cells Double Positive (DP) for the markers CD4 and CD8 that express very low levels of Notch1 showed major expression changes in pathways controlling the transition from physiology to disease. Further correlation of the data to ChIP-Seq data from the same cell populations led us to identify a hitherto unknown antagonism of the Notch1 oncogenic pathway and the polycomb complex (PRC2) in leukemia. Importantly exome sequencing in primary samples from human patients with T-ALL revealed that the PRC2 complex is frequently mutated and inactivated, further supporting the tumor suppressor role of the complex in this disease.
Publication Title
Genetic inactivation of the polycomb repressive complex 2 in T cell acute lymphoblastic leukemia.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 53 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Transgenic expression of TLX1 induces T-cell leukemias in mice.
Publication Title
The TLX1 oncogene drives aneuploidy in T cell transformation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The very low density lipoprotein receptor (VLDLR) is a multi-ligand receptor that mediates pleiotropic biological processes, such as brain development.
Publication Title
The very low density lipoprotein receptor attenuates house dust mite-induced airway inflammation by suppressing dendritic cell-mediated adaptive immune responses.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 28 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Medulloblastoma is the most common form of malignant paediatric brain tumour and is the leading cause of childhood cancer related mortality. The four molecular subgroups of medulloblastoma that have been identified WNT, SHH, Group 3 and Group 4 - have molecular and topographical characteristics suggestive of different cells of origin. Definitive identification of the cell(s) of origin of the medulloblastoma subgroups, particularly the poorer prognosis Group 3 and Group 4 medulloblastoma, is critical to understand the pathogenesis of the disease, and ultimately for the development of more effective treatment options.
Publication Title
Gene expression analyses of the spatio-temporal relationships of human medulloblastoma subgroups during early human neurogenesis.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We compared the gene expression profile from a group of children with T-cell acute lymphoblastic leukamia who remained in continuous complete remission (CCR) (n = 7) with that from a group who relapsed (n = 5), using Affymetrix HG-U133A arrays. Using the decision-tree based supervised learning algorithm Random Forest (RF), genes were ranked with respect to their ability to discriminate between patients who remained in CCR and those who relapsed. From the 300 top-ranked probe sets 9 genes were selected for further investigation and validation in an independent cohort of 25 T-ALL patients using quantitative real time polymerase chain reaction.
Publication Title
Identification of novel molecular prognostic markers for paediatric T-cell acute lymphoblastic leukaemia.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Subject
View Samples- Homo sapiens
- 23 Downloadable Samples
- IlluminaHiSeq2500
Description
We evaluated changes in mRNA stability and transcription using 4sU metabolic pulse labeling across a four hour time course following activation of Jurkat T cells with PMA and PHA Overall design: Measurement of total mRNA (T) and 4sU labeled mRNA (IP) in three biological replicates at five time points: prior to activation (U) and the first four hours after activation (1-4)
Publication Title
Functional coordination and HuR-mediated regulation of mRNA stability during T cell activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos taurus
- 10 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
To identify transcriptional markers for beef traits related to meat tenderness and moisture, we measured the transcriptome of the Longissimus dorsi skeletal muscle in 10 Korean native cattle (KNC). We analyzed the correlation between the beef transcriptome and measurements of four different beef traits, shear force (SF), water holding capacity (WHC), cooking loss (CL), and loin eye area (LEA). We obtained non-overlapping and unique panels of genes showing strong correlations (|r| > 0.8) with SF, WHC, CL, and LEA, respectively. Functional studies of these genes indicated that SF was mainly related to energy metabolism, and LEA to rRNA processing. Interestingly, our data suggested that WHC is influenced by protein metabolism. Overall, the skeletal muscle transcriptome pointed to the importance of energy and protein metabolism in determining meat quality after the aging process. The panels of transcripts for beef traits may be useful for predicting meat tenderness and moisture.
Publication Title
Characterization of beef transcripts correlated with tenderness and moisture.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Combinatorial ETS1-dependent control of oncogenic NOTCH1 enhancers in T-cell leukemia.
Sample Metadata Fields
Sex, Specimen part, Disease, Cell line
View Samples