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GSE66336
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Transcriptomes of differentiated cells of the conditionally immortalized mouse podocyte cell line SVI (Schiwek et al., Kidney Int. 66: 91-101, 2004) were determined as described in Warsow et al. (Kidney Int. 84: 104-115, 2013) after application of mechanical stress (Endlich et al., J. Am. Soc. Nephrol. 12: 413-422, 2001) as compared to control conditions.
Publication Title
Mechanical stress enhances CD9 expression in cultured podocytes.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
The Philadelphia chromosome (Ph) encoding the oncogenic BCR-ABL1 kinase defines a subset of ALL with a particularly unfavorable prognosis. Acute lymphoblastic leukemia (ALL) cells are derived from B cell precursors in most cases and typically carry rearranged immunglobulin heavy chain (IGH) variable (V) region genes devoid of somatic mutations. Somatic hypermutation is restricted to mature germinal center B cells and depends on activation-induced cytidine deaminase (AID). Studying AID expression in 108 cases of ALL, we detected AID mRNA in 24 of 28 Ph-positive ALLs as compared to 6 of 80 Ph-negative ALLs. Forced expression of BCR-ABL1 in Ph-negative ALL cells and inhibition of the BCR-ABL1-kinase showed that aberrant expression of AID depends on BCR-ABL1 kinase activity. Consistent with aberrant AID expression in Ph-positive ALL, IGH V region genes and BCL6 were mutated in many Ph-positive but unmutated in most Ph-negative cases. In addition, AID introduced DNA-single-strand breaks within the tumor suppressor gene CDKN2B in Ph-positive ALL cells, which was sensitive to BCR-ABL1 kinase inhibition and silencing of AID expression by RNA interference. These findings identify AID as a BCR-ABL1-induced mutator in Ph-positive ALL cells, which may be relevant with respect to the particularly unfavorable prognosis of this leukemia subset.
Publication Title
Activation-induced cytidine deaminase acts as a mutator in BCR-ABL1-transformed acute lymphoblastic leukemia cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Differentiation of hematopoietic stem cells (HSCs) is regulated by a concert of different transcription factors (TFs). A disturbed function of TFs can be the basis of (pre)malignancies such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Growth Factor Independence 1b (Gfi1b) is a repressing TF with a key role in quiescence of HSCs and emergence and maturation of erythrocytes and platelets. Here, we show that low expression of GFI1B in blast cells is associated with inferior prognosis of MDS and AML patients. Using mouse models with either reduced expression or conditional deletion of Gfi1b, crossed with a mouse model reflecting human MDS or AML, we demonstrate that AML development was accelerated with heterozygous loss of Gfi1b, and latency was further decreased when Gfi1b was conditionally deleted. Loss of Gfi1b significantly enhanced stemness of leukemic cells with upregulation of genes fundamentally involved in leukemia development. On a molecular level, we found that loss of Gfi1b not only increased the levels of reactive oxygen species (ROS) but also induced gene expression changes of key AML pathways such as the p38/AKT pathway. These results demonstrate that Gfi1b functions as an oncosuppressor in MDS/AML development.
Publication Title
Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
PURPOSE. During retinal degeneration, Müller glia cells respond to photoreceptor loss by undergoing reactive gliosis, with both detrimental and beneficial effects. Increasing our knowledge of the complex molecular response of Müller cells to retinal degeneration is thus essential for the development of new therapeutic strategies. The purpose of this work was to identify new factors involved in Müller cell response to photoreceptor cell death. METHODS. Whole transcriptome sequencing was performed from wild-type and degenerating rd10 mouse retinas at P30. The changes in mRNA abundance for several deregulated genes were assessed by RT-qPCR. Protein expression level and retinal cellular localization were determined by western-blot and immunohistochemistry, respectively. RESULTS. Pathway-level analysis from whole transcriptomic data revealed the Hippo/YAP pathway as one of the main signaling pathways altered in response to photoreceptor degeneration in rd10 retinas. We found that downstream effectors of this pathway, YAP and TEAD1, are specifically expressed in Müller cells and that their expression, at both the mRNA and protein levels, is increased in rd10 reactive Müller glia after the onset of photoreceptor degeneration. The expression of Ctgf and Cyr61, two target genes of the transcriptional YAP/TEAD complex, is also upregulated following photoreceptor loss. CONCLUSIONS. This work reveals for the first time that YAP and TEAD1, key downstream effectors of the Hippo pathway, are specifically expressed in Müller cells. We also uncovered a deregulation of the expression and activity of Hippo/YAP pathway components in reactive Müller cells under pathological conditions. Overall design: Retinal samples were harvested from C57Bl6/J and rd10 mouse retina at postnatal days 30 for whole transcriptome sequencing (RNAseq). Each sample included 2 frozen retina and experiments were performed in triplicate. RNA-seq transcriptome libraries were constructed from 1 ug of total RNA.
Publication Title
Retinal Degeneration Triggers the Activation of YAP/TEAD in Reactive Müller Cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This study addresses long-term effects of clinically relevant regimens of radiation in human glioma stem cells. Our investigations reveal a strikingly diverse spectrum of changes in cell behavior, gene expression patterns and tumor-propagating capacities evoked by radiation in different types of glioma stem cells. Evidence is provided that degree of cellular plasticity but not the propensity to self-renew is an important factor influencing radiation-induced changes in the tumor-propagating capacity of glioma stem cells. Gene expression analyses indicate that paralell transcriptomic responses to radiation underlie similarity of clinically relevant cellular outcomes such as the ability to promote tumor growth after radiation. Our findings underscore the importance of longitudinal characterizations of molecular and cellular responses evoked by cytotoxic treatrments in glioma stem cells.
Publication Title
Diversity of Clinically Relevant Outcomes Resulting from Hypofractionated Radiation in Human Glioma Stem Cells Mirrors Distinct Patterns of Transcriptomic Changes.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
Photoreceptor degeneration is the central event leading to visual impairment or blindness in most retinal diseases. However, the discovery of safe and effective therapeutic strategies conferring photoreceptor protection remains challenging. A systems pharmacology approach, synergistically targeting distinct cellular pathways could provide an effective strategy for evaluating, preventing or treating retinal dystrophies. Here this concept was investigated using a mouse model of light-induced retinal degeneration. We show that a combination of FDA-approved drugs acting on different G protein-coupled receptors in a synergistic manner could protect retinas against light-induced degeneration when each drug in the combination treatment was administered at a sub-therapeutic dose. Furthermore, transcriptome analyses demonstrated that such combined treatments also preserved patterns of retinal gene expression more characteristic of the normal retina than did single therapies at higher doses. The current study thus supports a new systems pharmacology approach that may extend to other complex neurodegenerative disorders in addition to retinal diseases. Overall design: Male and female Abca4-/-Rdh8-/- at the age of 4- to 6-weeks were used for the current study. All mice were housed and maintained in a 12 h light (=10 lux)/12 h dark cyclic environment in the Animal Resource Center at the School of Medicine, Case Western Reserve University (CWRU). Bright light-induced retinal damage was generated by exposing Abca4-/-Rdh8-/- mice to white light delivered at 10,000 lux (150 W spiral lamp, Commercial Electric) for 30 min. All indicated treatments were administered by intraperitoneal injection 30 min prior to bright light exposure and retinas collected one day later. Single compounds and their tested doses were: 2-Bromo-a-ergocryptine methanesulfonate salt (BRM), metoprolol tartrate (MTP), tamsulosin (TAM), and doxazosin (DOX). Combined treatments were: BRM, MTP and TAM (BMT), or MTP, DOX, and BRM (MDB). Processed data files (linked as series supplementary files): DE_combined.txt; Significant differential expression results from the combined pretreatment experiment. DE_mono.txt; Significant differential expression results from the mono pretreatment experiment. eXpress_counts_combined.txt; Quantitation output from eXpress of effective counts from the combined pretreatment experiment. eXpress_counts_mono.txt; Quantitation output from eXpress of effective counts from the mono pretreatment experiment. eXpress_fpkm_combined.txt; Quantitation output from eXpress of fpkm values from the combined pretreatment experiment. eXpress_fpkm_mono.txt; Quantitation output from eXpress of fpkm values from the mono pretreatment experiment. normalized_fpkm_combined.txt; TMM normalized fpkm values from the combined pretreatment experiment. normalized_fpkm_mono.txt; TMM normalized fpkm values from the mono pretreatment experiment.
Publication Title
Synergistically acting agonists and antagonists of G protein-coupled receptors prevent photoreceptor cell degeneration.
Sample Metadata Fields
Specimen part, Subject, Compound
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To characterize human bone marrow plasma cells that express or lack CD19 on a molecular level, we compared the global gene expression of primary CD38high/CD138+ plasma cells with or without CD19 expression.
Publication Title
A unique population of IgG-expressing plasma cells lacking CD19 is enriched in human bone marrow.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2500
Description
Goals of the study was to compare transcripional and phenotypic response of mouse intestinal organoid cultures to the KRAS(G12V) or BRAF(V600E)oncogenes. Overall design: Two biological replicates of organoids with transgenic luc-tdTomato, KRAS(G12V)-tdTomato, BRAF(V600E)-tdTomato were analysed by RNA-Seq By comparing 7-10 x 10E7 50bp paired end reads per library we identify transcriptional alterations in the intestinal epithelium following expression of each oncogene
Publication Title
Cell type-dependent differential activation of ERK by oncogenic KRAS in colon cancer and intestinal epithelium.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Vanin1, a regulator of vitamin B5 metabolism, is expressed by sarcoma tumors. We evaluated its impact on sarcoma growth by using sarcoma cell lines derived from p16p19Vnn1-deficient mice and further transduced with an oncogenic RasV12 oncogene (R tumors) in the presence or not of a catalytically active (VR tumors) or mutated (VdR tumors) Vnn1 isoform.
Publication Title
Vnn1 pantetheinase limits the Warburg effect and sarcoma growth by rescuing mitochondrial activity.
Sample Metadata Fields
Specimen part, Cell line
View Samples