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SRP058490
Homo sapiens
8 Downloadable Samples
IonTorrentProton
Description
The canonical Wnt pathway plays a central role in stem cell maintenance, differentiation and proliferation in the intestinal epithelium. Constitutive, aberrant activity of the TCF4/ß-catenin transcriptional complex is the primary transforming factor in colorectal cancer. Despite significant recent inroads, the full complement of Wnt target genes and the mechanisms of regulation remain incompletely understood. Here we identify a nuclear long non-coding RNA, termed WiNTRLINC1, as a direct target of TCF4/ß-catenin in colorectal cancer cells. WiNTRLINC1 positively regulates the expression of its close neighbor ASCL2, a transcription factor that controls intestinal stem cell fate. WiNTRLINC1 interacts with TCF4/ß-catenin to mediate the juxtaposition/physical contact of its own promoter with the regulatory regions of ASCL2. ASCL2, in turn, regulates WiNTRLINC1 expression. This feedforward regulatory loop controls stem cell-related gene expression and is highly amplified in colorectal cancer. Overall design: Derivatives of Ls174T colon cancer cells, overexpressing the Tet repressor were used for the construction of inducible overexpressing a shRNA against the WiNTRLINC1 long non coding RNA upon treatment with doxyxycline. siRNAs against WiNTRLINC1 were designed with the siDesign center tool from Dharmacon and their sequences were used for the construction of the shRNA stem loop structure as described in EMBO Rep. 2003 Jun;4(6):609-15. The modified pTER vector was used as a backbone for constructing the shRNA cassette as described in EMBO Rep. 2003 Jun;4(6):609-15. Positive cell clones were screened with RT-PCR in order to validate the efficiency of the knockdown of WiNTRLINC1. The Ls174T derivative cell line inducibly overexpressing a shRNA against ASCL2 has been described previously in Cell. 2009 Mar 6;136(5):903-12. RNA deep sequencing was performed in the WiNTRLINC1 KD and ASCL2 KD cells compared to controls cells in order to detect changes in gene expression due to the loss of either WiNTRLINC1 or ASCL2.
Publication Title
A Positive Regulatory Loop between a Wnt-Regulated Non-coding RNA and ASCL2 Controls Intestinal Stem Cell Fate.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray-based gene expression data were generated from RNA from Ls174T colorectal carcinoma cell lines in which Wnt-dependent transcriptional activity can be abrogated by inducible overexpression of a dominant-negative form of Tcf4 or siRNA against -catenin.
Publication Title
Integrated genome-wide analysis of transcription factor occupancy, RNA polymerase II binding and steady-state RNA levels identify differentially regulated functional gene classes.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 86 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Time series of eleven breast cancer samples subjected to different cold ischemic stress of up to 3 hr post tumor excision.
Publication Title
Effects of tissue handling on RNA integrity and microarray measurements from resected breast cancers.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Surprisingly few pathways signal between cells, raising questions about mechanisms for tissue-specific responses. In particular, Wnt ligands signal in many mammalian tissues, including the intestinal epithelium, where constitutive signaling causes cancer. Genome-wide analysis of DNA cis-regulatory regions bound by the intestine-restricted transcription factor CDX2 in colonic cells uncovered highly significant over-representation of sequences that bind TCF4, a transcriptional effector of intestinal Wnt signaling. Chromatin immunoprecipitation confirmed TCF4 occupancy at most such sites and co-occupancy of CDX2 and TCF4 across short distances. A region spanning the single nucleotide polymorphism rs6983267, which lies within a MYC enhancer and confers colorectal cancer risk in humans, represented one of many co-occupied sites. Co-occupancy correlated with intestine-specific gene expression and CDX2 loss reduced TCF4 binding.These results implicate CDX2 in directing TCF4 binding in intestinal cells. Co-occupancy of regulatory regions by signal-effector and tissue-restricted transcription factors may represent a general mechanism for ubiquitous signaling pathways to achieve tissue-specific outcomes.
Publication Title
TCF4 and CDX2, major transcription factors for intestinal function, converge on the same cis-regulatory regions.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Bos taurus
- 19 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Thecal tissue forms a layer around the follicle just prior to antral stage and grows with the follicle (containing an oocyte) as it matures. The innermost component (theca interna) supplies hormones and other factors necessary to the growth and development of the granulosa and oocyte. Most follicles regress and die (become atretic) at the antral stage, and this process as well as development of the follicle are undoubtedly influenced by the theca.
Publication Title
Transcriptome profiling of the theca interna in transition from small to large antral ovarian follicles.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 15 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
The growth of the mammalian ovarian follicle requires the formation of a fluid filled antrum, and maturation and differentiation of the ovarian granulosa cells, largely under the control of Follicle Stimulating Hormone (FSH). Many follicles will regress and die by a process called atresia at this early antral stage. We therefore decided to analyse the gene expression profiles of granulosa cells cultured in the presence or absence of FSH and Tumour Necrosis Factor-alpha (TNF), an apoptotic factor, to simulate the key influences. Different concentratons of FSH and TNFa in granulosa culture were used to determine effective conditions via estradiol and progesterone production, and cell number.
Publication Title
The global effect of follicle-stimulating hormone and tumour necrosis factor α on gene expression in cultured bovine ovarian granulosa cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 64 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Comparison of concordance in single and multi-gene genomic indices from data generated by two different laboratories (MD Anderson Cancer Center (MDA) and Jules Bordet Institute (JBI)) and on two different Affymetrix platforms (U113A and U133_Plus2).
Publication Title
Genomic index of sensitivity to endocrine therapy for breast cancer.
Sample Metadata Fields
Specimen part, Subject
View Samples- Bos taurus
- 18 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Granulosa cells mature and die as ovarian follicles enlarge and die (undergo atresia) under the influence of hormones and intrafollicular factors. Later in follicular development, a fluid-filled antrum is formed, a process which is accompanied by a high rate of atresia. These small antral follicles (5 mm or less in diameter in the cow) contain granulosa of 2 different phenotypes, rounded or columnar, whereas follicles larger than 5 mm have the rounded phenotype only. Prior to ovulation, in larger follicles greater than 10 mm in size, the granulosa begin to migrate and differentiate in preparation for oocyte release and formation of the corpus luteum.
Publication Title
Transcriptome profiling of granulosa cells from bovine ovarian follicles during atresia.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 18 Downloadable Samples
- Bovine Gene 1.0 ST Array (bovgene10st)
Description
The ovary has specialized stromal compartments, including the tunica albuginea, interstitial stroma and theca interna, which develops concurrently with the follicular antrum. To characterize the molecular determinants of these compartments, stroma adjacent to preantral follicles (pre-theca), interstitium and tunica albuginea were laser microdissected (n = 4 per group) and theca interna was dissected from bovine antral follicles (n = 6).
Publication Title
Transcriptome analyses of ovarian stroma: tunica albuginea, interstitium and theca interna.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens, Rattus norvegicus
- 1314 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Rat Genome 230 2.0 Array (rat2302), Affymetrix Human Genome U133A Array (hgu133a), Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The MAQC-II Project: A comprehensive study of common practices for the development and validation of microarray-based predictive models
Publication Title
Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.
Sample Metadata Fields
Sex, Age, Specimen part, Race, Compound
View Samples