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GSE143007
Homo sapiens
18 Downloadable Samples
Affymetrix Clariom S Human array (clariomshuman)
Description
The combined influence of oncogenic drivers, genomic instability, and/or DNA damage repair deficiencies increases replication stress in cancer. Cells with high replication stress rely on the upregulation of checkpoints like those governed by CHK1 for survival. Previous studies of the CHK1 inhibitor prexasertib demonstrated activity across multiple cancer types. Therefore, we sought to (1) identify markers of prexasertib sensitivity and (2) define the molecular mechanism(s) of intrinsic and acquired resistance using preclinical models representing multiple tumor types. Our findings indicate that while cyclin E dysregulation is a driving mechanism of prexasertib response, biomarkers associated with this aberration lack sufficient predictive power to render them clinically actionable for patient selection. Transcriptome analysis of a pan-cancer cell line panel and in vivo models revealed an association between expression of E2F target genes and prexasertib sensitivity and identified innate immunity genes associated with prexasertib resistance. Functional RNAi studies supported a causal role of replication fork components as modulators of prexasertib response. Mechanisms which protect cells from oncogene-induced replication stress may safeguard tumors from such stress induced by a CHK1 inhibitor, resulting in acquired drug resistance. Furthermore, resistance to prexasertib may be shaped by innate immunity.
Publication Title
A pan-cancer transcriptome analysis identifies replication fork and innate immunity genes as modifiers of response to the CHK1 inhibitor prexasertib.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
Huge efforts are made to engineer safe and efficient genome editing tools. An alternative might be the harnessing of ADAR-mediated RNA editing. We now present the engineering of chemically optimized antisense oligonucleotides that recruit endogenous human ADARs to edit endogenous transcripts in a simple and programmable way, an approach we refer to as RESTORE. Notably, RESTORE was markedly precise, and there was no evidence for perturbation of the natural editing homeostasis. We applied RESTORE to a panel of standard human cell lines, but also to several human primary cells including hepatocytes. In contrast to other RNA and DNA editing strategies, this approach requires only the administration of an oligonucleotide, circumvents the ectopic expression of proteins, and thus represents an attractive platform for drug development. In this respect we have shown the repair of the PiZZ mutation causing a1-antitrypsin deficiency and the editing of phosphotyrosine 701 in STAT1. Overall design: Identification of off-target editing events and Interferon-a influence in HeLa cell line transfected with an ASO for RNA editing by RNA-Seq, 2 samples (ASO +/- IFN) , 2 control sample (+/-IFN), 2 biologically independent experiments for each sample, 8 samples in total
Publication Title
Precise RNA editing by recruiting endogenous ADARs with antisense oligonucleotides.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Cutaneous malignant melanoma is among the most deadly human cancers, broadly resistant to most clinical therapies. A majority of patients with BRAFV600E melanomas respond well to inhibitors such as vemurafenib, but all ultimately relapse. Moreover, there are no viable treatment options available for other non-BRAF melanoma subtypes in the clinic. A key to improving treatment options lies in a better understanding of mechanisms underlying melanoma progression, which are complex and heterogeneous. In this study we perform gene expression profilling of highly and poorly malignant melanocytic tumors from genetically engineered mouse models to discover important drivers of cancer progression.
Publication Title
Integrated Genomics Identifies miR-32/MCL-1 Pathway as a Critical Driver of Melanomagenesis: Implications for miR-Replacement and Combination Therapy.
Sample Metadata Fields
Specimen part
View Samples- Xenopus laevis
- 5 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
The response of ectodermal explants, neuralized by noggin and treated with cycloheximide, following activation of hormone-inducible zic1 injected into the parent embryos compared to those from beta globin injected embryos as controls, is expected to provide information on the direct targets of the Zic1 transcription factor.
Publication Title
A microarray screen for direct targets of Zic1 identifies an aquaporin gene, aqp-3b, expressed in the neural folds.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The effect of dietary calcium and dairy proteins on adipose tissue gene expression profile in diet induced obesity
Publication Title
Effect of dietary calcium and dairy proteins on the adipose tissue gene expression profile in diet-induced obesity.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 21 Downloadable Samples
- Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
The zebrafish has the capacity to regenerate its heart after severe injury. While the function of a few genes during this process has been studied, we are far from fully understanding how genes interact to coordinate heart regeneration. To enable systematic insights into this phenomenon, we generated and integrated a dynamic co-expression network of heart regeneration in the zebrafish and linked systems-level properties to the underlying molecular events. Across multiple post-injury time points, the network displays topological attributes of biological relevance. We show that regeneration steps are mediated by modules of transcriptionally coordinated genes, and by genes acting as network hubs. We also established direct associations between hubs and validated drivers of heart regeneration with murine and human orthologs. The resulting models and interactive analysis tools are available at http://infused.vital-it.ch. Using a worked example, we demonstrate the usefulness of this unique open resource for hypothesis generation and in silico screening for genes involved in heart regeneration.
Publication Title
Analysis of the dynamic co-expression network of heart regeneration in the zebrafish.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix HT Human Genome U133A Array (hthgu133a)
Description
U87MG is a glioblastoma cell line that shows substantial heterogeneity despite long-term passaging.
Publication Title
Dynamic epigenetic regulation of glioblastoma tumorigenicity through LSD1 modulation of MYC expression.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Dyskeratosis congenita (DC) is an inherited multi-system disorder, characterized by oral leukoplakia, nail dystrophy, and abnormal skin pigmentation, as well as high rates of bone marrow failure, solid tumors, and other medical problems such as osteopenia. DC and telomere biology disorders (collectively referred to as TBD here) are caused by germline mutations in telomere biology genes leading to very short telomeres and limited proliferative potential of hematopoietic stem cells. We found that skeletal stem cells (SSCs) within the bone marrow stromal cell population (BMSCs, also known as bone marrow-derived mesenchymal stem cells), may contribute to the hematological phenotype.
Publication Title
Molecular profile of clonal strains of human skeletal stem/progenitor cells with different potencies.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
In this study we obtained gene expression profiles of MCFS and parental MCF7 cell lines using Illumina microarrays
Publication Title
In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Down syndrome is the most common form of genetic mental retardation. How Trisomy 21 causes mental retardation remains unclear and its effects on adult neurogenesis have not been addressed. To gain insight into the mechanisms causing mental retardation we used microarrays to investigate gene expression differences between Ts1Cje (a mouse model of Down syndrome) and C57BL/6 littermate control neurospheres. The neurospheres were generated from neural stem cells and progenitors isolated from the lateral walls of the lateral ventricles from adult mice.
Publication Title
Gene network disruptions and neurogenesis defects in the adult Ts1Cje mouse model of Down syndrome.
Sample Metadata Fields
Sex, Disease
View Samples