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SRP075759
Homo sapiens
29 Downloadable Samples
Illumina HiSeq 2500
Description
The mechanisms underlying hepatoblastoma are not well defined. To address this, we generated transcriptomic profiles of normal, background, and hepatoblastoma liver samples from patients aged 0.01 months to 6 years, using RNA-sequencing. Hepatoblasoma was histologically confirmed. Here we focus on the elevation of stem cell markers and the loss of tumor suppressor proteins leading to the development of hepatoblastoma in very young children. Overall design: Hepatic mRNA profiles of normal (n=3), background (n=6), and hepatoblastoma (n=23) tissues were generated through RNAsequencing using the Illumina HiSeq2500.
Publication Title
PARP1 activation increases expression of modified tumor suppressors and pathways underlying development of aggressive hepatoblastoma.
Sample Metadata Fields
Sex, Specimen part, Subject
View Samples- Mus musculus, Homo sapiens
- 7 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Multiple layers of transcriptional regulation by PLZF in NKT-cell development.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
The murine model of Lyme disease provides a unique opportunity to study the localized host response to similar stimulus, B. burgdorferi, in the joints of mice destined to develop severe arthritis (C3H) or mild disease (C57BL/6). Pathways associated with the response to infection and the development of Lyme arthritis were identified by global gene expression patterns using oligonucleotide microarrays. A robust induction of IFN responsive genes was observed in severely arthritic C3H mice at one week of infection, which was absent from mildly arthritic C57BL/6 mice. In contrast, infected C57BL/6 mice displayed a novel expression profile characterized by genes involved in epidermal differentiation and wound repair, which were decreased in the joints of C3H mice. These expression patterns were associated with disease state rather than inherent differences between C3H and C57BL/6 mice, as C57BL/6-IL10-/- mice infected with B. burgdorferi develop more severe arthritis that C57BL/6 mice and displayed an early gene expression profile similar to C3H mice. Gene expression profiles at two and four weeks post infection revealed a common response of all strains that was likely to be important for the host defense to B. burgdorferi and mediated by NF-kB-dependent signaling. The gene expression profiles identified in this study add to the current understanding of the host response to B. burgdorferi and identify two novel pathways that may be involved in regulating the severity of Lyme arthritis.
Publication Title
Gene expression profiling reveals unique pathways associated with differential severity of lyme arthritis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 7 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To identify genes that require PLZF for their regulation in NKT cells, we compared the developmental stages of thymic NKT cells from wildtype and PLZF-deficient mice
Publication Title
Multiple layers of transcriptional regulation by PLZF in NKT-cell development.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Description
To identify regulators of homeostatic eosinophilopoiesis in mice, we took a global approach to identify genome-wide transcriptome and epigenome changes that occur during homeostasis at critical developmental stages, including eosinophil-lineage commitment (eosinophil progenitor [EoP] compared to granulocyte-monocyte progenitor [GMP]) and lineage maturation (eosinophil compared to EoP). Our analyses revealed markedly greater transcriptome alterations associated with eosinophil maturation (1199 genes) compared to eosinophil-lineage commitment (490 genes), highlighting the greater transcriptional investment necessary for differentiation. Our analyses also delineated a 976 gene eosinophil-lineage transcriptome that included a repertoire of 56 transcription factors, many of which have never previously been associated with eosinophils. Epigenomic studies revealed that genes that were specifically induced with eosinophil-lineage commitment in EoPs were “poised” with active chromatin marks in GMPs, despite not being expressed in GMPs. In contrast, a majority of the genes that were highly and specifically induced with maturation in eosinophils was not associated with poised chromatin, suggesting distinct epigenetic regulation between genes induced with lineage commitment compared to genes induced with cell maturation during eosinophil development. Overall design: RNA Seq and H3K4me3 distribution of GMPs, EoPs and eosinophils sorted from Balb/c bone marrow. RNA Seq libraries were prepared from 2 independent sorts of each cell type (GMP, EoPs, Eosinophils [Eos]). ChIP Seq was performed with chromatin from one sort of each cell type.
Publication Title
Transcription Factor Repertoire of Homeostatic Eosinophilopoiesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression profile of joint tissue from C3H and interval specific congenic mouse lines (ISCL) following infection with Borrelia burgdorferi
Publication Title
Interval-specific congenic lines reveal quantitative trait Loci with penetrant lyme arthritis phenotypes on chromosomes 5, 11, and 12.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
The physiological responses to B cell receptors (BCR) and Toll-like receptors (TLRs) so vital to immunity are well known but the transcriptional signatures and regulatory mechanisms that initiate activation and release cells from quiescence remain unclear. Here, we show that BCR- or TLR-mediated activation of B cells involves a large shared transcriptional signature and a smaller subset of distinct signal-specific transcriptional responses. Signal-specific transcription is observable within 2 hours of ligand exposure; suggesting different modes of activation begin soon after ligand binding and long before the well-documented BCR and TLR-dependent physiological responses occur. Ligand-specific differences in regulatory mechanisms including RNA Pol II recruitment, activating (H3K4me3) and repressing (H3K27me3) histone marks, transcription factor binding sites in responsive gene promoters, and miRNA expression were observed. These results begin to define the transcriptional landscape of early B cell activation revealing more ligand-specific regulation and character than occurs much earlier than previously expected. Overall design: CD43- mouse resting B cells were stimulated with ligands against the B cell receptor and TLR4 (LPS). RNA-sequencing was performed to describe differential transcription and ChIP-sequencing was performed to describe regulatory mechanism responses.
Publication Title
Divergence of transcriptional landscape occurs early in B cell activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 94 Downloadable Samples
- Illumina HiSeq 2500
Description
Delineating key HSC regulators is of significant interest for informing the treatment of hematologic malignancy. While HSC activity is enhanced by overexpression of SKI, the transforming growth factor-beta (TGFß) signaling antagonist corepressor, its requirement in HSC is unknown. Here we reveal a profound defect in Ski-/- HSC fitness but not specification. Transcriptionally, Ski-/- HSC exhibited striking upregulation of TGFb superfamily signaling and splicing alterations. As these are both common aspects of myelodysplastic-syndrome (MDS) pathobiology with prognostic value, we investigated the role of SKI in MDS. A SKI-correlated gene signature defines a subset of low-risk MDS patients with active TGFß signaling and deregulated RNA splicing (e.g. CSF3R). The apparent paradox of Ski-/- HSC sharing molecular aspects of MDS with elevated SKI-mRNA is resolved by miR-21 targeting of SKI in MDS. We conclude that miR-21-mediated loss of SKI contributes to early stage MDS pathogenesis by activating TGFß signaling and alternative splicing while hindering HSC fitness. Overall design: Single cell RNA seq of transplanted fetal liver-derived hematopoietic stem cells
Publication Title
<i>SKI</i> controls MDS-associated chronic TGF-β signaling, aberrant splicing, and stem cell fitness.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 23 Downloadable Samples
- Illumina HiSeq 2000
Description
T lymphocytes are essential contributors to the adaptive immune system and consist of multiple lineages that serve various effector and regulatory roles. As such, precise control of gene expression is essential to the proper development and function of these cells. Previously, we identified Snai2 and Snai3 as being essential regulators of immune tolerance partly due to the impaired function of CD4+ regulatory T cells in Snai2/3 conditional double knockout mice. Here we extend those previous findings using a bone marrow transplantation model to provide an environmentally unbiased view of the molecular changes imparted onto various T lymphocyte populations once Snai2 and Snai3 are deleted. The data presented here demonstrate that Snai2 and Snai3 transcriptionally regulate the cellular fitness and functionality of not only CD4+ regulatory T cells but effector CD8a+ and CD4+ conventional T cells as well. This is achieved through the modulation of gene sets unique to each cell type and includes transcriptional targets relevant to the survival and function of each T cell lineage. As such, Snai2 and Snai3 are essential regulators of T cell immunobiology. Overall design: GFP- CD3e+ CD8a+ CD4-, GFP- CD3e+ CD8a- CD4+ CD25- and GFP- CD3e+ CD8a- CD4+ CD25+ T cells were isolated from spleens of UBC-GFP mice transplanted with WT or cDKO lineage-depleted donor bone marrow following lethal irradiation of recipient mice. RNA-seq was performed on 3-4 biological replicates from each genotype for all T cell populations analyzed.
Publication Title
Snai2 and Snai3 transcriptionally regulate cellular fitness and functionality of T cell lineages through distinct gene programs.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Chromosome 5q deletions (del(5q)) are common in high-risk (HR) Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML); however, the gene regulatory networks that sustain these aggressive diseases are unknown. Reduced miR-146a expression in del(5q) HR-MDS/AML and miR-146a-/- hematopoietic stem/progenitor cells (HSPC) results in TRAF6/NF- activation. Increased survival and proliferation of HSPC from miR-146alow HR-MDS/AML is sustained by a neighboring haploid gene, SQSTM1 (p62), expressed from the intact 5q allele. Overexpression of p62 from the intact allele occurs through NF-B-dependent feedforward signaling mediated by miR-146a deficiency. p62 is necessary for TRAF6-mediated NF-B signaling, as disrupting the p62-TRAF6 signaling complex results in cell cycle arrest and apoptosis of MDS/AML cells. Thus, del(5q) HR-MDS/AML employs an intrachromosomal gene network involving loss of miR-146a and haploid overexpression of p62 via NF-B to sustain TRAF6/NF-B signaling for cell survival and proliferation. Interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q) MDS/AML.
Publication Title
Myeloid malignancies with chromosome 5q deletions acquire a dependency on an intrachromosomal NF-κB gene network.
Sample Metadata Fields
Sex, Specimen part
View Samples