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Mus musculus
10 Downloadable Samples
Description
Environmental cadmium, with a high average dietary intake, is a severe public health risk. However, the long-term health implications of environmental exposure to cadmium in different life stages remain unclear.
Publication Title
Sex-Dependent Effects of Cadmium Exposure in Early Life on Gut Microbiota and Fat Accumulation in Mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
SMRT (silencing mediator of retinoid and thyroid hormone receptors) is recruited by numerous transcription factors to mediate lineage and signal dependent transcriptional repression. We generated a knock-in mutation in the receptor interaction domain (RID) of SMRT (SMRTmRID) that solely disrupts its interaction with nuclear hormone receptors. SMRTmRID-derived 3T3-MEFs display a dramatically increased adipogenic capacity and accelerated differentiation rate. We measured global gene expression in wild-type versus SMRTmRID-derived 3T3-MEFs in the undifferentiated state to examine which pathways were altered. Our results demonstrate that SMRT-RID dependent repression is a key determinant of the adipogenic set point.
Publication Title
SMRT repression of nuclear receptors controls the adipogenic set point and metabolic homeostasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 25 Downloadable Samples
Description
MicroRNAs have emerged as major genetic elements in the genesis and suppression of cancer. Here, multi-dimensional cancer genome analysis and validation has defined a novel Glioblastoma Multiforme (GBM) tumor suppressor pathway and mechanism of action centered on Quaking (QK), a member of the STAR family of RNA-binding proteins. Combined functional, biochemical and computational studies establish that p53 directly regulates QK gene expression, QK protein binds and stabilizes miR-20a of the cancer-relevant miR-17-92 cluster, and miR-20a in turn functions to regulate TGFR2 and the TGF signaling network. Linkage of these pathway components is supported by their genome and expression status across GBM specimens and by their gain- and loss-of-function interactions in in vitro and in vivo complementation studies. This p53-QK-miR-20a axis expands our understanding of the p53 tumor suppression network in cancer and reveals a novel tumor suppression mechanism involving regulation of specific cancer-relevant microRNAs.
Publication Title
STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Identify potential QK-regulated mRNAs and linked pathways by comparing the transcriptional profiles of shGFP- and shQK-transduced Ink4a/Arf-/- Pten-/- primary mouse astrocytes
Publication Title
STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Identify potential miR-20a regulated mRNAs and linked pathways in the setting of QK knockdown by comparing the transcriptional profiles of shQK-transduced primary mouse Ink4a/Arf-/- Pten-/- astrocytes together with miR-20a or a scrambled miRNA control (miR-NT)
Publication Title
STAR RNA-binding protein Quaking suppresses cancer via stabilization of specific miRNA.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
Description
FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis
Publication Title
FoxOs cooperatively regulate diverse pathways governing neural stem cell homeostasis.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Glioblastoma (GBM) is a highly lethal brain tumor presenting as one of two subtypes with distinct clinical histories and molecular profiles. The primary GBM subtype presents acutely as high-grade disease that typically harbors EGFR, PTEN and Ink4a/Arf mutations, and the secondary GBM subtype evolves from the slow progression of low-grade disease that classically possesses PDGF and p53 events1. Here, we show that concomitant CNS-specific deletion of p53 and Pten in the mouse CNS generates a penetrant acute-onset high-grade malignant glioma phenotype with striking clinical, pathological and molecular resemblance to primary GBM in humans. This genetic observation prompted p53 and PTEN mutational analysis in human primary GBM, demonstrating unexpectedly frequent inactivating mutations of p53 as well the expected PTEN mutations. Integrated transcriptomic profling, in silico promoter analysis and functional studies of murine neural stem cells (NSCs) established that dual, but not singular, inactivation of p53 and Pten promotes an undifferentiated state with high renewal potential and drives elevated c-Myc levels and its associated signature. Functional studies validated increased c-Myc activity as a potent contributor to the impaired differentiation and enhanced renewal of p53-Pten null NSCs as well as tumor neurospheres (TNSs) derived from this model. c-Myc also serves to maintain robust tumorigenic potential of p53-Pten null TNSs. These murine modeling studies, together with confirmatory transcriptomic/promoter studies in human primary GBM, validate a pathogenetic role of a common tumor suppressor mutation profile in human primary GBM and establish c-Myc as a key target for cooperative actions of p53 and Pten in the regulation of normal and malignant stem/progenitor cell differentiation, self-renewal and tumorigenic potential.
Publication Title
p53 and Pten control neural and glioma stem/progenitor cell renewal and differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 35 Downloadable Samples
Description
Tertiary lymphoid organs (TLOs) emerge in response to nonresolving inflammation but their roles in adaptive immunity remain unknown. Here, we explored artery TLOs (ATLOs) to delineate atherosclerosis T cell responses in apoe-/- mice during aging. Though the T cell repertoire showed systemic age-associated contractions in size and modifications in subtype composition and activation, wt and apoe-/- mice were equally affected. In contrast, ATLOs - but not wt aortae, apoe-/- aorta segments without ATLOs or atherosclerotic plaques - promoted T cell recruitment, altered characteristics of T cell motility, primed and imprinted T cells in situ, generated CD4+/FoxP3-, CD4+/FoxP3+, CD8+/FoxP3- effector and central memory cells, and converted nave CD4+/FoxP3- T cells into induced Treg cells. ATLOs also showed substantially increased antigen presentation capability by conventional dendritic cells (DCs) and monocyte-derived DCs but not by plasmacytoid DCs. Thus, the senescent immune system specifically employs ATLOs to control dichotomic atherosclerosis T cell immune responses. We assembled transcriptome maps of wt and apoe-/- aortae and aorta-draining RLNs and identified ATLOs as major sites of atherosclerosis-specific T cell responses during aging: Transcriptome atlases of wt and apoe-/- abdominal aortae and associated draining RLNs were constructed from laser capture microdissection (LCM)-based whole genome mRNA expression microarrays yielding 6 maps: wt adventitia (tissue-1); wt RLN (tissue-2); apoe-/- ATLOs (tissue-3); apoe-/- RLN (tissue-4); apoe-/- adventitia without adjacent plaques (tissue-5), and plaques (tissue-6). Several two-tissue comparisons within the transcriptome atlases are noteworthy: Unexpectedly, transcriptomes of wt and apoe-/- RLNs were virtually identical; additonal data revealed that transcriptomes of RLNs were strikingly similar to those of inguinal LNs which do not drain the aorta adventitia (as shown of India ink injection experiments of surgically exposed aortae); in sharp contrast, wt adventitia versus ATLOs revealed 1405 differentially expressed transcripts many of which encoded members of GO terms immune response and inflammatory response; the ATLO-plaque comparison also showed > 1000 differentially expressed transcripts; however, wt adventitia versus apoe-/- adventitia without plaque showed few genes (< 5 % of differentially expressed transcripts of the wt adventitia-ATLO comparison). Thus, the aorta transcriptome atlases support the conclusion that neither aorta-draining apoe-/- RLNs nor ILNs participate in atherosclerosis-specific T cell responses. In addition, they demonstrate that T cell responses in the diseased aorta are highly territorialized. Finally, these data show that the immune responses carried out in ATLOs differ significantly from those carried out in plaques. We next identified three major clusters within the transcriptome atlases through ANOVA analyses and application of strict filters: An adventitia cluster, a plaque/ATLO cluster, and a LN/plaque cluster. The total number of differentially expressed genes in each cluster were examined for GO terms immune response, inflammatory response, T cell activation, positive regulation of T cell response, and T cell proliferation. Within the adventitia cluster, similarities of transcriptomes of wt adventitia and apoe-/- adventitia without associated plaque versus ATLOs indicate that a robust number of immune response-regulating genes are selectively expressed in ATLOs which are located within a distance of few m of the adventitia without associated plaques indicating a very high degree of territoriality of the atherosclerosis T cell response. Furthermore, unlike the total number of differentially regulated transcripts, the majority of transcripts among GO terms immune response and inflammatory response, was up-regulated. Inspection of the plaque/ATLO cluster provided further information: The majority of immune response regulating genes where expressed at a higher level in ATLOs when compared to plaques though plaques also contained a significant number of immune response regulating genes; the reverse is true for genes regulating inflammation. Finally, the lymph node cluster revealed that though the majority of immune response regulating genes resides in both wt and apoe-/- RLNs (with little differences between them) ATLOs express a selected set of immune response regulating genes at a higher level when compared to LNs. In addition, the inflammatory component of ATLOs when compared to LNs is documented by the finding that many more genes regulating inflammation reside in ATLOs even when compared to those of plaques.
Publication Title
Generation of Aorta Transcript Atlases of Wild-Type and Apolipoprotein E-null Mice by Laser Capture Microdissection-Based mRNA Expression Microarrays.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Danio rerio
- 5 Downloadable Samples
Description
In the early zebrafish embryo, the developing genome profile can be interfered with by exposure to pentachlorophenol, and some specific sets of genes are up-regulated or down-regulated. We used microarrays to detail the global program of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during this process.
Publication Title
Pentachlorophenol exposure causes Warburg-like effects in zebrafish embryos at gastrulation stage.
Sample Metadata Fields
Specimen part, Treatment
View Samples
GSE19320- Danio rerio
- 1 Downloadable Sample
Description
Gene expression profiling of zebrafish early eye development on 3 to 5 days post fertilization (dpf)
Publication Title
Integrating multiple genome annotation databases improves the interpretation of microarray gene expression data.
Sample Metadata Fields
Specimen part
View Samples