Filters
Technology
Platform
GSE26621
Mus musculus
6 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Cancer metastasis is a fetal problem that claims life of over 90% of cancer patients. It is hypothesized that cancer stem cells (CSCs) mediate cancer metastasis and such cells are often resistant to chemotherapy. Studying BRCA1 associated cancers, we found that CSCs form fillopodia and protrusions enriching for active forms of ezrin/radixin/moesin proteins and they have a much higher potential to metastasize than non-CSCs. Microarray analysis indicated that many pathways related to cell adhesion, extracellular matrix and cytoskeleton were differentially regulated in CSCs. Although inhibition of cytoskeleton remodeling by cisplatin treatment retarded CSC motility and cancer metastasis, drug resistant cancers eventually emerge containing markedly increased number of CSCs. This event is at least partially attributed to the activation of PI3K/mTOR signaling, and can be significantly inhibited by the treatment of rapamycin. These results provide strong evidence that cytoskeletal rearrangement and PI3K/mTOR signaling play a distinct role in mediating CSC mobility and viability, and blocking of both pathways in CSCs synergistically inhibits primary and metastatic cancer growth in BRCA1 associated tumors.
Publication Title
Synergistic therapeutic effect of cisplatin and phosphatidylinositol 3-kinase (PI3K) inhibitors in cancer growth and metastasis of Brca1 mutant tumors.
Sample Metadata Fields
Specimen part
View Samples- Gallus gallus
- 8 Downloadable Samples
- Affymetrix Chicken Genome Array (chicken)
Description
The inner ear develops from a patch of thickened cranial ectoderm adjacent to the hindbrain called the otic placode. Studies in a number of vertebrate species suggest that the initial steps in induction of the otic placode are regulated by members of the Fibroblast Growth Factor (FGF) family, and that inhibition of FGF signaling can prevent otic placode formation. To better understand the genetic pathways activated by FGF signaling during otic placode induction, we performed microarray experiments to estimate the proportion of chicken otic placode genes that can be up-regulated by the FGF pathway in a simple culture model of otic placode induction. Surprisingly, we find that FGF is only sufficient to induce about 15% of chick otic placode-specific genes in our experimental system. However, pharmacological blockade of the FGF pathway in cultured chick embryos showed that although FGF signaling was not sufficient to induce the majority of otic placode-specific genes, it was still necessary for their expression in vivo. These inhibitor experiments further suggest that the early steps in otic placode induction regulated by FGF signaling occur through the MAP kinase pathway. Although our work suggests that FGF signaling is necessary for otic placode induction, it demonstrates that other unidentified signaling pathways are required to co-operate with FGF signaling to induce the full otic placode program.
Publication Title
Analysis of FGF-dependent and FGF-independent pathways in otic placode induction.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Myotonic dystrophes (DM), the most common adult muscular dystrophy, are the first recognized examples of RNA-mediated diseases in which expression of mutant RNAs containing expanded CUG or CCUG repeats interfere with the splicing of other mRNAs. Using whole-genome microarrays, we found that alternative splicing of the BIN1 mRNA is altered in DM skeletal muscle tissues, resulting in the expression of an inactive form of BIN1 deprived of phosphoinositide-binding and membrane-tubulating activities. BIN1 is involved in tubular invaginations of the plasma membrane and is essential for biogenesis of the muscle T-tubules, which are specialized skeletal muscle membrane structures essential to correct excitation-contraction (E-C) coupling. Mutations in the BIN1 gene cause centronuclear myopathy (CNM) that shares some histopathological features with DM, and both diseases are characterized by muscle weakness. Consistent with a loss-of-function of BIN1, muscle T-tubules were altered in DM patients, and membrane tubulation was restored upon expression of the correct splicing form of BIN1 in DM muscle cells. By deciphering the mechanism of BIN1 splicing mis-regulation we demonstrate that the splicing regulator, MBNL1, which is sequestered by expanded CUG and CCUG in DM, binds the BIN1 pre-mRNA and regulates directly its alternative splicing. Finally, reproducing BIN1 splicing alteration in mice is sufficient to reproduce the DM features of T-tubule alterations and muscle weakness. We propose that alteration of BIN1 alternative splicing regulation leads to muscle weakness, a predominant pathological feature of DM.
Publication Title
Misregulated alternative splicing of BIN1 is associated with T tubule alterations and muscle weakness in myotonic dystrophy.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 60 Downloadable Samples
Illumina HiSeq 2000
Description
Xist is indispensable for X chromosome inactivation (XCI) in female mammalian cells. However, how Xist RNA directs chromosome-wide transcriptional inactivation of the X chromosome is largely unknown. Here, to study chromosome inactivation by Xist, we generated a system where ectopic Xist expression can be induced from several genomic contexts in aneuploid mouse ES cells. We found that ectopic Xist expression from any location on the X chromosome faithfully recapitulated endogenous XCI, showing the potency of Xist to initiate XCI. Genes that escape XCI remain consistently transcriptionally active upon ectopic XCI, regardless of their position relative to Xist transgenes, and the enrichment of CTCF at their promoters is implicated in directing XCI escape. Xist expression from autosomes facilitates their transcriptional silencing to different degrees, and gene density in proximity of the Xist transcription locus plays a central role in determining the efficiency of gene inactivation. We also show that the enrichment of LINE elements together with a specific chromatin environment facilitates Xist-mediated silencing of both X-linked and autosomal genes. These findings provide new insights into the epigenetic mechanisms that mediate XCI and identify genomic features that promote Xist-mediated chromosome-wide gene inactivation Overall design: 60 RNA-seq from mouse embryonic stem cells and fully differentiated neurons in which ectopic Xist epression is either triggered (plus samples) or not (minus samples) upon doxycycline treatment.
Publication Title
Genetic and epigenetic features direct differential efficiency of Xist-mediated silencing at X-chromosomal and autosomal locations.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
How the parental genomes of the very specialized sperm and oocyte cells are remodelled upon fertilization to confer totipotency has remained a tantalizing open questions. Indeed, in the case of mammals, the parental genomes undergo dramatic reprogramming upon fertilization, including differential dynamics of histone post-translational modifications. The roles of histone modifying enzymes in this process, which are maternally provided, are only just starting to emerge. Here, we explore the function of the oocyte inherited pool of Lsd1/Kdm1a, which encodes a histone H3K4 and K9 demethylase, during early mouse development. Maternal deficiency of Lsd1/Kdm1a results in developmental arrest by the two-cell stage, associated with dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns depending on its demethylase activity. At the transcriptional level, two major changes occur. On one hand, switch from maternal-to-zygotic program fails to be induced. On the other hand, LINE-1 retrotransposons are not properly silenced, along with evidences for increased LINE-1 activity. We propose that Lsd1/Kdm1a is involved in the correct establishment of epigenetic information harboured by histones and is involved in the initiation of new pattern of genome expression driving early mouse development and preserving genome integrity Overall design: RNA-seq of invidual mouse two-cell stage embryos
Publication Title
Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 14 Downloadable Samples
- Illumina HiSeq 2500
Description
How the parental genomes of the very specialized sperm and oocyte cells are remodelled upon fertilization to confer totipotency has remained a tantalizing open questions. Indeed, in the case of mammals, the parental genomes undergo dramatic reprogramming upon fertilization, including differential dynamics of histone post-translational modifications. The roles of histone modifying enzymes in this process, which are maternally provided, are only just starting to emerge. Here, we explore the function of the oocyte inherited pool of Lsd1/Kdm1a, which encodes a histone H3K4 and K9 demethylase, during early mouse development. Maternal deficiency of Lsd1/Kdm1a results in developmental arrest by the two-cell stage, associated with dramatic and stepwise alterations in H3K9 and H3K4 methylation patterns depending on its demethylase activity. At the transcriptional level, two major changes occur. On one hand, switch from maternal-to-zygotic program fails to be induced. On the other hand, LINE-1 retrotransposons are not properly silenced, along with evidences for increased LINE-1 activity. We propose that Lsd1/Kdm1a is involved in the correct establishment of epigenetic information harboured by histones and is involved in the initiation of new pattern of genome expression driving early mouse development and preserving genome integrity Overall design: RNA-seq of invidual mouse oocytes
Publication Title
Maternal LSD1/KDM1A is an essential regulator of chromatin and transcription landscapes during zygotic genome activation.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2500
Description
We performed single-cell RNA-seq on CD4 T cells isolated from the tonsils of one healthy donor. We used the 10x chromium technology. Overall design: Tonsil CD4 T cells were enriched by negative selection using magnetic beads. Cell populations (CXCR5+PD-1low T cells, CXCR5+PD-1int T cells and CXCR5+PD-1high T cells ) were further isolated by cell sorting. Cellular suspensions (3500 cells) were loaded on a 10X Chromium instrument (10X Genomics) according to manufacturer's protocol.
Publication Title
Human lymphoid organ cDC2 and macrophages play complementary roles in T follicular helper responses.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 1 Downloadable Sample
- Illumina HiSeq 2500
Description
We performed single-cell RNA-seq on CD14+ cells isolated from the tonsils of one healthy donor. We used the 10x chromium technology. Overall design: Tonsil phagocytes were prepared by centrifugation on a Ficoll gradient. Dendritic cells and macrophages were enriched by negative selection using magnetic beads. Cell populations were further isolated by cell sorting. Cellular suspensions (3500 cells) were loaded on a 10X Chromium instrument (10X Genomics) according to manufacturer's protocol.
Publication Title
Human lymphoid organ cDC2 and macrophages play complementary roles in T follicular helper responses.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 41 Downloadable Samples
- Illumina HiSeq 2500
Description
using RNA-seq we characterized gene expression changes occuring upon knockout of BAP1, ASXL1, ASXL2, ASXL1/2 or Polycomb genes RING1B and EZH2. We also investigated the response to retinoic acid treatment in wild-type and BAP1 KO cells. Overall design: Examination of transcript abundance in wild-type HAP1 cells and in 9 different HAP1-mutated cell lines as well as upon retinoic acid treatment in wild-type and BAP1 KO cells. Two biological replicated were performed for each condition.
Publication Title
BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Characterization of gene expression changes occuring upon knockout of RING1A, RING1B, and BAP1. Overall design: Four Samples
Publication Title
BAP1 complex promotes transcription by opposing PRC1-mediated H2A ubiquitylation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples