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SRP052064
Mus musculus
2 Downloadable Samples
Illumina HiSeq 2000
Description
To examine Ikaros tumor suppressor mechanisms, we have utilized inducible RNAi to dynamically restore endogenous Ikaros expression in T-ALL driven by its knockdown. This causes rapid transcriptional repression of Notch1 and associated targets including Myc, even in leukemias harboring spontaneous activating Notch1 mutations (producing aberrant ICN1) similar to those found in 60% of human T-ALL. Ikaros restoration results in sustained regression of Notch1-wild type leukemias while endogenous or engineered ICN1 expression promotes rapid disease relapse, indicating that ICN1 functionally antagonizes Ikaros in T-ALL. Overall design: RNA-seq was performed on T-ALL (Vav-tTA;TRE-GFP-shIkaros primary leukemia ALL211) cells isolated from two untreated and two 3-day Dox-treated mice.
Publication Title
Activated Notch counteracts Ikaros tumor suppression in mouse and human T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
To examine Ikaros tumor suppressor mechanisms, we have utilized inducible RNAi to dynamically restore endogenous Ikaros expression in T-ALL driven by its knockdown. This causes rapid transcriptional repression of Notch1 and associated targets including Myc, even in leukemias harboring spontaneous activating Notch1 mutations (producing aberrant ICN1) similar to those found in 60% of human T-ALL. Ikaros restoration results in sustained regression of Notch1-wild type leukemias while endogenous or engineered ICN1 expression promotes rapid disease relapse, indicating that ICN1 functionally antagonizes Ikaros in T-ALL. Overall design: RNA-seq was performed on T-ALL (Vav-tTA;TRE-GFP-shIkaros primary leukemia ALL65) cells isolated from three untreated and three 3-day Dox-treated mice. There were two sequencing runs of each RNA sample.
Publication Title
Activated Notch counteracts Ikaros tumor suppression in mouse and human T-cell acute lymphoblastic leukemia.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
The inhibitor of DNA binding 2 (Id2) is essential for NK cell development with its canonical role in this pathway being to antagonize E-proteins, silencing E-box gene expression and subsequent commitment to the T and B cell lineages. However, how E-box genes prevent NK cell development and homeostasis remains enigmatic. Here we identify a key role for Id2 in regulating the threshold for IL-15 receptor signaling and homeostasis of NK cells by repressing multiple E-protein target genes including Socs3. Deletion of Id2 in mature NK cells was incompatible with their homeostasis due to impaired IL-15 receptor signaling. Id2-null NK cells displayed impaired IL-15 mediated JAK1/STAT5 phosphorylation, compromised metabolic function and enhanced apoptosis. Remarkably, Id2-null NK cell homeostasis could be fully rescued in vivo by IL-15 receptor stimulation and partially rescued by genetic ablation of Socs3. During normal NK cell maturation we observed an inverse correlation between the expression levels of E-protein target genes and Id2. These results shift the current paradigm on the role of Id2, indicating that it is not only required to antagonize E-proteins during NK cell commitment, but constantly required to titrate E-protein activity to regulate NK cell fitness and responsiveness to IL-15. Overall design: Transcriptional profiling of wild type and Id2-null natural killer (NK) cells using RNA sequencing
Publication Title
The Helix-Loop-Helix Protein ID2 Governs NK Cell Fate by Tuning Their Sensitivity to Interleukin-15.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 38 Downloadable Samples
- IlluminaHiSeq2500
Description
Tissue-resident memory T cells (Trm) are non-circulating memory T cells that localize to portals of pathogen entry such as the skin, gut and lung where they provide efficient early protection against reinfection. Trm are characterized by a molecular profile that actively prevents egress from peripheral sites including the constitutive expression of the lectin CD69 and down-regulation of the chemokine receptor (CCR)7 and sphingosine-1-phosphate receptor 1 (S1PR1). This program is partially mediated by down-regulation of the transcription factor KLF2; however, to date no transcriptional regulator specific to Trm has been identified. Here we show that the Blimp1 related transcription factor Hobit is specifically upregulated in Trm and together with Blimp1, mediates the development and maintenance of Trm in various tissues including skin, gut, liver and kidney. Importantly, we found that the Hobit/Blimp1 transcriptional module is also required for other tissue-resident lymphocytes including Natural Killer T (NKT) cells and liver tissue-resident NK cells (trNK). We show that these populations share a universal transcriptional program with Trm instructed by Hobit and Blimp1 that includes the repression of CCR7, S1PR1 and KLF2 thereby enforcing tissue retention. Our results identify Hobit and Blimp1 as major common regulators that drive the differentiation of distinct populations of tissue-resident lymphocytes. Overall design: RNA-seq data were generated for multiple tissues in mice to investigate global expression difference between resident and circulating cells.
Publication Title
Hobit and Blimp1 instruct a universal transcriptional program of tissue residency in lymphocytes.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 1500
Description
Lymphocytic Choriomeningitis Virus (LCMV) specific CD8+ T cells (P14) were transferred into congenic WT mice followed by LCMV(DOCILE) infection. CXCR5-expressing (CXCR5+) or CXCR5 non-expressing (CXCR5-) P14 were purified on day 8 after infection, and total mRNA were sequenced from these populations. mRNA of P14 from uninfected mice (Naive P14) was also sequenced. Overall design: Examination of mRNA level in CXCR5 expressing P14 (CXCR5+P14) and non-expressing P14 (CXCR5-P14) from LCMV infected mice day 8 post infection. mRNA of P14 from uninfected mice (Naïve P14) was also examined.
Publication Title
CXCR5(+) follicular cytotoxic T cells control viral infection in B cell follicles.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 34 Downloadable Samples
- IlluminaHiSeq2500
Description
We report a time course of RNA-seq data from wild-type embryonic stem cells and embryonic stem cells in which the cardiogenic transcription factors ZNF503, ZEB2 and NKX2-5 are depleted with shRNAs differentiating along the cardiac lineage. Overall design: Biological replicates of RNA-seq data from embryonic stem cells differentiating along the cardiac lineage.
Publication Title
An Orthologous Epigenetic Gene Expression Signature Derived from Differentiating Embryonic Stem Cells Identifies Regulators of Cardiogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
To gain a deep understanding of mRNA turnover dynamics in mammalian cells, we pulse labeled newly synthesized RNA in 3t3 cells for 2 h with 4sU. RNA samples were fractionated into the newly synthesized and pre-existing fractions. Both fractions and the total RNA sample were analyzed by mRNA sequencing. We estimated mRNA half-lives based on the ratios of newly synthesized RNA/total RNA ratio and the preexisting RNA/total RNA.
Publication Title
Global quantification of mammalian gene expression control.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 48 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target.
Sample Metadata Fields
Sex, Age, Specimen part, Disease stage
View Samples- Homo sapiens
- 48 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Adrenocortical carcinoma (ACC) is associated with poor survival rates. The objective of the study was to analyze ACC gene expression profiling data prognostic biomarkers and novel therapeutic targets.
Publication Title
PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target.
Sample Metadata Fields
Sex, Disease stage
View Samples- Drosophila melanogaster
- 9 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Cardiogenesis involves multiple biological processes acting in concert during development, a coordination achieved by the regulation of diverse cardiac genes by a finite set of transcription factors (TFs). Previous work from our laboratory identified the roles of two Forkhead TFs, Checkpoint suppressor homologue (CHES-1-like) and Jumeau (Jumu) in governing cardiac progenitor cell divisions by regulating Polo kinase activity. These TFs were also implicated in the regulation of numerous other cardiac genes. Here we show that these two Forkhead TFs play an additional and mutually redundant role in specifying the cardiac mesoderm (CM): eliminating the functions of both CHES-1-like and jumu in the same embryo results in defective hearts with missing hemisegments. Our observations indicate that this process is mediated by the Forkhead TFs regulating the fibroblast growth factor receptor Heartless (Htl) and the Wnt receptor Frizzled (Fz), both previously known to function in cardiac progenitor specification: CHES-1-like and jumu exhibit synergistic genetic interactions with htl and fz in CM specification, thereby implying function through the same genetic pathways, and transcriptionally activate the expression of both receptor-encoding genes. Furthermore, ectopic overexpression of either htl or fz in the mesoderm partially rescues the defective CM specification phenotype seen in embryos doubly homozygous for mutations in jumu and CHES-1-like. Together, these data emphasize the functional redundancy that leads to robustness in the cardiac progenitor specification process mediated by Forkhead TFs regulating the expression of signaling pathway receptors, and illustrate the pleiotropic functions of this class of TFs in different aspects of cardiogenesis.
Publication Title
Two forkhead transcription factors regulate the division of cardiac progenitor cells by a Polo-dependent pathway.
Sample Metadata Fields
Specimen part
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