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GSE56402
Mus musculus
8 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
We established and characterized a new recessive mutant mouse line kta41 with a point mutation in Scube3 at position 882. The mutant line was detected by screening for morphological abnormalities in the Munich ENU-mutagenesis program. The mutation was mapped by microsatellite markers to mouse chromosome 17, between markers D17MIT29 and D17MIT101. Candidate gene approaches failed due to the low recombination frequency and the high number of genes within the mapped interval. Whole genome sequencing approaches revealed a C to A transversion on position 882 in Scube3 that leads to a missense mutation in the protein (Asn294Lys). We did a broad phenotypic analysis of the mutant mouse line in the German Mouse Clinic (GMC), and followed up the found alterations by detailed phenotypic characterization. Scube3-kta41-/- mice show a series of phenotypic alterations, mainly in the skeleton, behavior and neurological abnormalities as well as changes in physiology, metabolism and immune status.
Publication Title
The First Scube3 Mutant Mouse Line with Pleiotropic Phenotypic Alterations.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
We previously found that KLF4, a gene highly expressed in adult prostate stem cells, blocks the progression of indolent intraepithelial prostatic lesions into aggressive and rapidly growing tumors. To test whether this anti-cancer effect of KLF4 can also prevent prostate cancer-induced damage to the bone, we ablated KLF4 in human PC3 prostate cancer cells using CRISPR/Cas9-mediated genome editing and compared their behavior to null cells transduced with a DOX inducible KLF4 expression system. KLF4 re-expression inhibited growth of PC3 null cells in monolayer and as colonies in soft agar in a dose-dependent manner. When injected into the mouse femurs, PC3 null cells proliferated rapidly, forming very large, invasive and osteolytic tumors. Induction of KLF4 expression in PC3 null cells immediately after their intra-femoral inoculation blocked the development of tumors while preserving the normal bone architecture. KLF4 re-expression in established PC3 bone tumors inhibited osteolytic effects of PC3 null cells, preventing bone fractures and inducing a significant osteogenic response with regions of new bone formation. Transcriptome analyses of PC3 cells with no or high KLF4 expression revealed KLF4-dependent osteolytic or osteogenic transcriptional programs, respectively. Importantly, these KLF4-dependent functions significantly overlapped with metastatic prostate cancers in patients. Overall design: Uninfected PC3 KLF4 wild-type cells and uninfected PC3 KLF4 null cells were grown for 48 hours and collected for RNA extraction. Another cohort of PC3 KLF4 null cells was infected with lentiviruses expressing a DOX inducible KLF4 expression construct (BFP-T2A-hKLF4) or the control empty vector (BFP-T2A). After 48 hours, DOX (10 ng/ml) was added to the culture medium to induce KLF4 expression. Control and KLF4-overexpressing cells were collected for RNA extraction after a 48-hour incubation with DOX. Total RNA was extracted using the RNeasy kit (Qiagen, CA, USA). RNA-Seq libraries were prepared with the TruSeq sample preparation kit (Illumina, CA, USA).
Publication Title
KLF4 as a rheostat of osteolysis and osteogenesis in prostate tumors in the bone.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To explore the molecular basis for TSC22D4 function in hepatic lipid homeostasis in vivo TSC22D4 was knocked down in the mouse liver using adenovirus and performed genome wide expression analysis.
Publication Title
TSC22D4 is a molecular output of hepatic wasting metabolism.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Tumor metastasis and lack of NKG2D ligand (NKG2DL) expression are associated with poor prognosis in patients with colon cancer. Here we found that spironolactone (SPIR), an FDA-approved diuretic drug with a long-term safety profile, can upregulate NKG2DL expression in multiple colon cancer cell lines by activating the ATM-Chk2-mediated checkpoint pathway, which in turn enhances tumor elimination by natural killer cells. SPIR can also upregulate the expression of metastasis-suppressor genes TIMP2 and TIMP3, thereby reducing tumor cell invasiveness. Although SPIR is an aldosterone antagonist, its anti-tumor effects are independent of the mineralocorticoid receptor pathway. Instead, by screening the human nuclear hormone receptor siRNA library, we identify retinoid X receptor gamma (RXR gamma) as being indispensable for the anti-tumor functions of SPIR. Collectively, our results strongly support the use of SPIR or other RXR gamma-agonists with minimal side effects for colon cancer prevention and therapy.
Publication Title
Modulation of NKG2D ligand expression and metastasis in tumors by spironolactone via RXRγ activation.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have employed whole genome microarray expression profiling to identify genes differentially expressed in cord blood purified neutrophils after a short-term exposure to peptidoglycan (PGN).
Publication Title
Expression profile of cord blood neutrophils and dysregulation of HSPA1A and OLR1 upon challenge by bacterial peptidoglycan.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
A high-resolution time series study of transcriptome dynamics following antimiR--mediated inhibition of miR-9 in a Hodgkin lymphoma cell-line revealed both general and miR-9 specific aspects of the miRNA--mediated post--transcriptional dynamic response.MiR-9 inhibition induced a multiphasic gene response, with an initial direct response at approximately 4 hours and multiple later responses which showed transcription factor enrichments indicative of indirect causally downstream responses, and an overall shift of gene product function from predominantly mRNA processing at early time points to translation at later time points.
Publication Title
Transcriptome dynamics of the microRNA inhibition response.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Thymocyte selection-associated high mobility group box protein family member 2 (TOX2) is a transcription factor belonging to the TOX family that shares a highly conserved high mobility group DNA binding domain with the other TOX members. While TOX1 has been shown to be an essential regulator of T-cell and natural killer (NK) cell differentiation in mice, little is known about the roles of the other TOX family members in lymphocyte development, particularly in humans. In this study, we found that TOX2 was preferentially expressed in mature human NK cells and was upregulated during in vitro differentiation of NK cells from human umbilical cord blood (UCB)derived CD34+ cells. Gene silencing of TOX2 intrinsically hindered the transition between early developmental stages of NK cells, while overexpression of TOX2 enhanced the development of mature NK cells from UCB CD34+ cells. We subsequently found that TOX2 was independent of ETS-1 but could directly upregulate the transcription of TBX21 (encoding T-BET). Overexpression of T-BET rescued the TOX2 knockdown phenotypes. Given the essential function of T-BET in NK cell differentiation, TOX2 therefore plays a crucial role in controlling normal NK cell development by acting upstream of TBX21 transcriptional regulation.
Publication Title
TOX2 regulates human natural killer cell development by controlling T-BET expression.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
An Hodgkin Lymphoma cell line have been treated with an LNA inhibitor for miR-9 or with a scramble LNA to identify miR-9 regulated pathways that could be important for Hodgkin Lymphoma pathogenesis.
Publication Title
Inhibition of miR-9 de-represses HuR and DICER1 and impairs Hodgkin lymphoma tumour outgrowth in vivo.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Samples were taken from surgically resected tumor specimens/metastases from patients with colorectal cancer. The expression profiles were determined using the Affymetrix GeneChip Human Exon 1.0 ST Array version 2.
Publication Title
Colorectal Cancer Cell Line Proteomes Are Representative of Primary Tumors and Predict Drug Sensitivity.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Danio rerio
- 6 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Eye development and photoreceptor maintenance requires the retinal pigment epithelium (RPE), a thin layer of cells that underlies the neural retina. Despite its importance, RPE development has not been studied by a genomic approach. A microarray expression profiling methodology was established in this study for studying RPE development. The intact retina with RPE attached was dissected from developing embryos, and differentially expressed genes in RPE were inferred by comparing the dissected tissues with retinas without RPE using microarray and statistical analyses. We found 8810 probesets to be significantly expressed in RPE at 52 hours post-fertilization (hpf), of which 1443 might have biologically meaningful expression levels. Further, 78 and 988 probesets were found to be significantly over- or under-expressed in RPE respectively compared to retina. Also, 79.2% (38/48) of the known over-expressed probesets have been independently validated as RPE-related transcripts. The results strongly suggest that this methodology can obtain in vivo RPE specific gene expression from the zebrafish embryos and identify novel RPE markers.
Publication Title
Gene expression profiling of zebrafish embryonic retinal pigment epithelium in vivo.
Sample Metadata Fields
Specimen part
View Samples