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GSE20070
Homo sapiens
2 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We have previously reported that elevated fibroblast growth factor-2 (FGF-2) expression is associated with tumor recurrence and reduced survival after surgical resection of esophageal cancer, and that these risks are reduced in tumors co-expressing an endogenous antisense (FGF-AS) RNA. In the present study we examined the role of the endogenous FGF-AS transcript in the regulation of FGF-2 expression in the human lung adenocarcinoma cell line, Seg-1. FGF-2 and FGF-AS were temporally and spatially co-localized in the cytoplasm of individual cells, and knock-down of either FGF-2 or FGF-AS by target specific siRNAs resulted in dose-dependent up-regulation of the complementary transcript and its encoded protein product. Using a luciferase reporter system we show that these effects are mediated by interaction of the endogenous antisense RNA with the 3UTR of the FGF-2 mRNA. Deletion mapping identified a 392 nt sequence in the 5823 nucleotide FGF-2 untranslated tail which is targeted by FGF-AS. siRNA-mediated knockdown of either FGF-AS or FGF-2 significantly increased the stability of the complementary partner mRNA, demonstrating that these mRNAs are mutually regulatory. Knockdown of FGF-AS also resulted in reduced expression of argonaute-2 (AGO-2) and a number of other elements of the endogenous microRNA/RNAi pathways. Conversely, siRNA-mediated knockdown of AGO-2 significantly increased the stability of the FGF-2 mRNA transcript, and the steady-state levels of both FGF-2 mRNA and protein, suggesting a role for AGO-2 in the regulation of FGF-2 expression.
Publication Title
Regulation of fibroblast growth factor-2 by an endogenous antisense RNA and by argonaute-2.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Folate-mediated one-carbon metabolism is required for purine, thymidylate, and S-adenosylmethionine synthesis. Impairments in folate metabolism diminish cellular methylation potential and genome stability. Cytoplasmic serine hydroxymethyl transferase (cSHMT) regulates partitioning between thymidylate and SAM biosynthesis. These experiments were designed to determine if mutations in cSHMT led to alterations in gene expression.
Publication Title
Shmt1 heterozygosity impairs folate-dependent thymidylate synthesis capacity and modifies risk of Apc(min)-mediated intestinal cancer risk.
Sample Metadata Fields
Age
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The metabolic pathways that underlie the association between folate deficiency and increased risk for colorectal cancer (CRC) remain unclear. We have studied the effect of C1THF synthase (encoded by the Mthfd1 gene) and dietary folate and choline on intestinal tumor development in Apcmin/+ mice and azoxymethane (AOM)-induced colon cancer in mice. Mthfd1 deficiency did not alter tumor number or load in Apcmin/+ mice, but did result in a decreased incidence of colon tumors. Conversely, Mthfd1 deficiency increased tumor number 3.5-fold and tumor load 2-fold in AOM-treated mice. Here we tested colons isolated from wildtype and Mthfd1-deficient animals for alterations in gene expression.
Publication Title
Mthfd1 is a modifier of chemically induced intestinal carcinogenesis.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 87 Downloadable Samples
Illumina HiSeq 3000, Illumina HiSeq 2500
Description
Mammalian genomes encode several hundred Krüppel-associated box zinc finger proteins (KRAB-ZFPs) that bind DNA in a sequence-specific manner through tandem arrays of C2H2-type zinc fingers and repress transcription via KRAB-dependent recruitment of the silencing cofactor KAP1. The KRAB-ZFP family rapidly amplified and diversified in mammals by segmental gene duplications, mutations, and zinc finger rearrangements likely in response to continued transposable element invasions, but the biological functions and in vivo requirement of these proteins has gone largely unexplored. We determined the genomic binding sites of 61 murine KRAB-ZFPs and genetically deleted five large KRAB-ZFP gene clusters encoding more than 100 of the approximately 360 mouse KRAB-ZFPs. We demonstrate that most KRAB-ZFPs bind to specific retrotransposon families and that many of these retrotransposons are transcriptionally activated in KRAB-ZFP cluster KO ESCs, licensing retrotransposon-derived enhancers to activate nearby genes. Overall design: RNA-seq analysis of KRAB-ZFP cluster KO ES cells and tissues.
Publication Title
KRAB-zinc finger protein gene expansion in response to active retrotransposons in the murine lineage.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Embryonic stem cell potency fluctuates with endogenous retrovirus activity.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We compared gene expression from 2C::tomato+/- ES cells from Kdm1a wt and mutant ES cultures
Publication Title
Embryonic stem cell potency fluctuates with endogenous retrovirus activity.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
To determine gene expression in 2 cell stage embryos Overall design: 3 Replicates of litters of wild type 2 cell stage embryos
Publication Title
Embryonic stem cell potency fluctuates with endogenous retrovirus activity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
To measure gene expression difference between wt and g9A knockout ES cells Overall design: G9A TT2 ES cells (Yokochi et al) were treated with Veh. Or 4OHT (to delete G9A)
Publication Title
Embryonic stem cell potency fluctuates with endogenous retrovirus activity.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina Genome Analyzer II
Description
We identified/quantified genes and repeat elements enriched within 2C::tomato+ cells vs. 2C::tomato - cells Overall design: 2C::tomato + and - cells were collected by FACS for RNA-Seq analysis
Publication Title
Embryonic stem cell potency fluctuates with endogenous retrovirus activity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Mouse embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) exhibit a pluripotent developmental potential, contributing to all embryonic cell types, though rarely to extra-embryonic lineages. Unexpectedly, rare, totipotent-like stem cells have been identified in cultured ESC populations, suggesting the existence of a discrete molecular pathway that regulates the transition between totipotency and pluripotency in vitro. Here, we identify a single miRNA, miR-34a, whose deficiency in mouse pluripotent stem cells expands cell fate potential, giving rise to both embryonic and extra-embryonic lineages in vitro and in vivo. The expression profiles of the totipotent-like miR-34a-knockout murine pluripotent stem cells are characterized by a strong induction of MERVL endogenous retroviruses, a key molecular hallmark shared with totipotent mouse 2-cell blastomeres and totipotent-like mouse ESCs. In all three cell types, a subset of MERVL elements promotes the expression of specific isoforms of the proximal protein-coding genes. We demonstrate that miR-34a represses MERVL expression through transcriptional regulation, at least in part, by directly targeting the transcription factor GATA-binding protein 2 (Gata2). Since MERVL activation correlated precisely with the totipotent-like state, we hypothesized that the miR-34a/Gata2 pathway that regulates MERVL expression in ESCs/iPSCs also regulates the acquisition of totipotency in culture. Consistent with this hypothesis, gata2 knock-down in miR-34a-knockout mouse pluripotent stem cells not only reduced MERVL expression, but also abolished the expanded cell fate potential of these cells both in vitro and in vivo. Taken together, our findings not only provide key insights into the functional importance of miR-34a in restricting the totipotent cell fate potential of pluripotent stem cells, but also elucidate the underlying molecular basis by which miR-34a regulates the developmental potentials of ESCs/iPSCs. Overall design: Wildtype and miR-34a-deficient iPSCs, three biological replicates per group
Publication Title
Deficiency of microRNA <i>miR-34a</i> expands cell fate potential in pluripotent stem cells.
Sample Metadata Fields
No sample metadata fields
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