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SRP151720
Mus musculus
8 Downloadable Samples
Illumina HiSeq 2500
Description
During development, changes in gene transcription are accompanied by changes in chromatin modification but the order and causality of events often remain unclear. Here we address this question using X-chromosome inactivation (XCI), which entails chromosome-wide gene silencing and heterochromatin formation. We initiate XCI in female, mouse embryonic stem cells by inducing Xist expression and monitor subsequent changes in transcription and chromatin modification by allele-specific TTseq and ChIPseq respectively. An unprecedented temporal resolution has enabled us to define early alterations in chromatin that are induced upon Xist RNA coating. Xist-induced repression begins with histone deacetylation, which involves the histone deacetylase HDAC3 and occurs before efficient loss of H3K4me3 and H3K4me1 modifications. Polycomb-associated repressive histone marks accumulate rapidly, starting with PRC1-associated H2AK119Ub and followed by PRC2-associated H3K27me3. However, polycomb accumulates initially at large premarked domains, some of which correspond to Xist entry sites, and then spreads into genes. We also show that spreading can only ensue when transcriptional silencing has occurred. These results establish a detailed epigenomic time course for XCI and reveal a hierarchy of events with chromatin playing an important role in transcriptional silencing of the X chromosome. Overall design: RNAseq on WT and HDAC3 KO cell lines from TX1072 cell line. For WT and HDAC3KO samples RNAseq in 2 replicates (Rep1, Rep2) at 2 different times of DOX induction (0h, 24h).
Publication Title
The Implication of Early Chromatin Changes in X Chromosome Inactivation.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 33 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Currently there is no method available to predict response to farnesyltransferase inhibitors (FTI). We analyzed gene expression profiles from the bone marrow of patients from a phase 2 study of the FTI tipifarnib, in older adults with previously untreated acute myeloid leukemia (AML). The RASGRP1:APTX gene expression ratio was found to predict response to tipifarnib with the greatest accuracy. This two-gene ratio was validated by quantitative PCR (QPCR) in the newly diagnosed AML cohort. We further demonstrated that this classifier could predict response to tipifarnib in an independent set of 54 samples from relapsed or refractory AML, with a negative predictive value (NPV) and positive predictive value (PPV) of 92% and 28%, respectively (odds ratio of 4.4). The classifier also predicted for improved overall survival (154 vs 56 days, p = 0.0001), which was shown to be independent of other prognostic factors including a previously described gene expression classifier predictive of overall survival. Therefore, these data indicate that a two-gene expression assay may have utility in categorizing a population of AML patients who are more likely to respond to tipifarnib.
Publication Title
A 2-gene classifier for predicting response to the farnesyltransferase inhibitor tipifarnib in acute myeloid leukemia.
Sample Metadata Fields
Sex, Age, Disease
View Samples- Mus musculus
- 54 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The Melanoma-associated Antigen gene family (MAGE) generally encodes for tumour antigens. We recently have identified one of the MAGE gene members, Mageb16 to be highly expressed in undifferentiated murine embryonic stem cells (mESCs). The role of Mageb16 for the differentiation of the pluripotent stem cells is completely unknown. Here we demonstrate that Mageb16 (41 kDa) is distributed in cytosol and/or in surface membrane in undifferentiated mESCs. A transcriptome study was performed with differentiated short hairpin RNA (shRNA)-mediated Mageb16 knockdown (KD ESCs) and scrambled control (SCR) ESCs until a period of 22 days. Mageb16 KD ESCs mainly differentiated towards mesodermal derivatives such as cardiovascular lineages. Mesoderm-oriented differentiation initiated biological processes such as adipogenesis, osteogenesis, limb morphogenesis and spermatogenesis were significantly enriched in the differentiated Mageb16 KD ESCs. Cardiomyogenesis in differentiated KD mESCs was stronger when compared to differentiated SCR and wild mESCs. The expression of non-coding RNA (ncRNA) Lin28a and other epigenetic regulatory genes, nucleocytoplasmic trafficking and genes participating in spermatogenesis have also declined faster in the differentiating Mageb16 KD ESCs. We conclude that Mageb16 plays a crucial role for differentiation of ESCs, specifically to the mesodermal lineages. Regulative epigenetic networks and nucleocytoplasmic modifications induced by Mageb16 may play a role for the critical role of Mageb16 for the ESCs differentiation.
Publication Title
Depletion of Mageb16 induces differentiation of pluripotent stem cells predominantly into mesodermal derivatives.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Comparative analysis of Endodermal-like cell lines with demonstrated ability to support myocardial differentiation
Publication Title
A comparative analysis of extra-embryonic endoderm cell lines.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 110 Downloadable Samples
- Sentrix MouseRef-8 Expression BeadChip
Description
Linkage analysis of complex traits in mice is a powerful tool to find loci affecting the phenotype but it has a poor resolution making it difficult to identify the underlying genes. We show here, using whole genome association analysis of gene expression traits in an outbred mouse population, the MF1 stock, that mapping resolution is greatly increased as compared to linkage. The fact that eQTLs discovered in other crosses were replicated and successfully mapped with high resolution in this population provides a strong proof of concept. In addition, we show that this population is a useful resource to resolve the eQTL hotspots detected in other studies. Finally, we highlight the importance of correcting for population structure in whole genome association studies in the outbred stock.
Publication Title
High-resolution mapping of gene expression using association in an outbred mouse stock.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human mesenchymal stem cells (MSC) display a high potential for the development of novel treatment strategies for cartilage repair. However, the pathways involved in their differentiation to functional and non hypertrophic chondrocytes remain largely unknown, despite the work on embryologic development and the identification of key growth factors including members of the TGF, Hh, Wnt and FGF families. In this study, we asked if we could identify specific biological networks independently from the growth factor used (TGF-3 or BMP-2). To address this question, we used DNA microarrays and performed large-scale expression profiling of MSC at different time points during their chondral differentiation. By comparing these data with those obtained during their differentiation into osteoblasts and adipocytes, we identified 318 genes specific for chondrogenesis. We distributed the selected genes in 5 classes according to their kinetic of expression and used the Ingenuity software in order to identify new biological networks. We could reconstruct 3 phases for chondral differentiation, characterized by functional pathways. The first phase corresponds to cell attachment and apoptosis prevention with the up-regulation of 5 integrins, BCL6, NFIL3, RGS2 and down-regulation of CTGF and CYR61. The second phase is characterized by a proliferation/differentiation step with the continuous expression of MAF, PGF, HGMA1 or NOTCH3, CHI3L1, WNT5A, LEPR. Finally, the last step of differentiation/hypertrophy is characterized by expression of DKK1, APOD/E, SERPINF1 and TIMP4. These data propose new pathways to understand the complexity of MSC differentiation to chondrocytes and new potential targets for cell therapy applied to cartilage repair.
Publication Title
Gene expression profile of multipotent mesenchymal stromal cells: Identification of pathways common to TGFbeta3/BMP2-induced chondrogenesis.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 44 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The role of Striatin Interacting Protein 2 (Strip2) in differentiation of embryonic stem cells (ESCs) is still under debate. Strip2 silenced (KD) ESCs were differentiated for 4, 8, 12, and 16 days. We show that Strip2 is distributed in the perinucleus or nuclei of wild type (WT) undifferentiated ESCs, but is localized in high-density nuclear bodies in differentiated cells. CellNet analysis of microarray gene expression data for KD and scrambled control (SCR) embryoid bodies (EBs), as well as immunostainings of key pluripotent factors, demonstrated that KD ESCs remain undifferentiated. This occurs even in 16-day old EBs, which possessed a high tumorigenic potential. Correlated with very high expression levels of epigenetic regulator genes, Hat1 and Dnmt3, enzymatic activities of the histone acetyltransferase type B (HAT1) and DNA (cytosine-5)-methyltransferase 3 beta (DNMT3b) were higher in differentiated 16-day old KD EBs than in SCR or WT EBs. The expression levels of let-7, 290 and 302 microRNA families were opposed in KD ESCs, while KD EBs had levels comparable to WT and SCR ESCs during differentiation. This demonstrates that Strip2 is critical to the onset of differentiation, regulating expression of epigenetic regulators, HAT1 and DNMT3b, as well as microRNAs involved in pluripotency.
Publication Title
STRIP2 Is Indispensable for the Onset of Embryonic Stem Cell Differentiation.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 84 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
assess the efficacy of dual PI3K/mTOR inhibitor with anti-lymphoma activity as single agent and in combination
Publication Title
PQR309 Is a Novel Dual PI3K/mTOR Inhibitor with Preclinical Antitumor Activity in Lymphomas as a Single Agent and in Combination Therapy.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 61 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
assess the gene expression profiling of 61 cell lines
Publication Title
PQR309 Is a Novel Dual PI3K/mTOR Inhibitor with Preclinical Antitumor Activity in Lymphomas as a Single Agent and in Combination Therapy.
Sample Metadata Fields
Specimen part, Cell line
View Samples GSE12078- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To monitor global transcript changes after Paf1C depletion we transfected ESCs with esiRNA targeting Ctr9 and control esiRNA (Luc).
Publication Title
A genome-scale RNAi screen for Oct4 modulators defines a role of the Paf1 complex for embryonic stem cell identity.
Sample Metadata Fields
No sample metadata fields
View Samples