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Homo sapiens
5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The organization of mammalian DNA replication is poorly understood. We have produced genome-wide high-resolution dynamic maps of the timing of replication in human erythroid, mesenchymal and embryonic stem cells using TimEX, a method that relies on gaussian convolution of massive, highly redundant determinations of DNA copy number variations during S phase obtained using either high-density oligonucleotide tiling arrays or massively-parallel sequencing to produce replication timing profiles. We show that in untransformed human cells, timing of replication is highly regulated and highly synchronous, and that many genomic segments are replicated in temporal transition regions devoid of initiation where replication forks progress unidirectionally from origins that can be hundreds of kilobases away. Absence of initiation in one transition region is shown at the molecular level by SMARD analysis. Comparison of ES and erythroid cells replication patterns revealed that these cells replicate about 20% of their genome in different quarter of S phase and that ES cells replicate a larger proportion of their genome in early S phase than erythroid cells. Importantly, we detected a strong inverse relationship between timing of replication and distance to the closest expressed gene. This relationship can be used to predict tissue specific timing of replication profiles from expression data and genomic annotations. We also provide evidence that early origins of replication are preferentially located near highly expressed genes, that mid firing origins are located near moderately expressed genes and that late firing origins are located far from genes.
Publication Title
Predictable dynamic program of timing of DNA replication in human cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
2-methoxyestradiol (2ME2) induces mammary gland differentiation through amphiregulin-EGFR mediated signaling: molecular distinctions from the mammary gland of pregnant mice.High levels of 2ME2 are observed in the late stages of pregnancy. We investigated the role of 2ME2 on normal mammary gland development. Large scale gene expression assays were performed using Affymetrix GeneChips in pursuit of detailed molecular basis. (1) Mammary glands of wild type FVB mice administered 75 or 150 mg/kg of 2ME2 (2) Mammary glands of normal FVB/Nj mice (i) at day 16 of pregnancy, (ii) day 2 of lactation (iii) day 30 of post-lactation, and (3) mammary epithelial SCp2 cells after 6, 24 and 48 hours of 10 micromol 2ME2 treatment were examined. In vivo studies revealed that 2ME2 treatment up regulates the expression of amphiregulin. The clue to the role of 2ME2 in differentiation comes from studies in vitro which detected down regulation of inhibitor of differentiation (Id-1) gene and consequent up regulation of amphiregulin. The differentiation of E2 negative SCp2 cells by 2ME2 indicate estradiol independent mechanism. For details, please see our paper in Endocrinology 2006.
Publication Title
2-methoxyestradiol induces mammary gland differentiation through amphiregulin-epithelial growth factor receptor-mediated signaling: molecular distinctions from the mammary gland of pregnant mice.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Aberrant cell proliferation, a hallmark of most cancers, requires the escape from intrinsic antitumour barriers. Primary among these is the DNA damage response (DDR). In both cell culture-models and in early stages of tumorigenesis in vivo, activated oncogenes induce DNA replication stress and DNA double-strand breaks (DSBs), leading to DDR activation and p53-dependent apoptosis and/or senescence. The means by which tumour-initiating cells, also termed cancer stem cells (CSCs), circumvent this oncosuppressive response is unknown. Here we demonstrate that the ZEB1 transcription factor provides breast CSCs with the ability to withstand an aberrant mitogenic activity. Its forced expression in human mammary epithelial cells is sufficient to alleviate DNA replicative stress and to decrease the production of reactive oxygen species, an important contributor to DDR and oncogene-induced senescence. Consistently, human breast cancer cells with endogenous ZEB1 expression show two characteristic features: low levels of DSBs and DDR markers, reflecting mitigation of the DNA replication stress, and a low p53 mutation frequency, reflecting a weak selective pressure for inactivation. Using high-throughput sequencing analysis of controlled cellular models, we further demonstrate that ZEB1 delays the onset of structural chromosomal instability (CIN), a known consequence of replicative stress and prevents the emergence of chromosome 8p deletions and 8q amplifications, two prevalent abnormalities in high-grade breast cancers. Supporting these findings, ZEB1 expression discriminates human breast tumours by their copy number alterations (CNAs) and chromosome 8 aberrations. We propose that the tumorigenic potential of CSCs relies upon their unique capacity to tolerate oncogenic stimuli through the alleviation of DNA replication stress.
Publication Title
A stemness-related ZEB1-MSRB3 axis governs cellular pliancy and breast cancer genome stability.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Gene 2.0 ST Array (ragene20st)
Description
Regulation of homeostasis and development of cardiac muscle tissues is controlled by a core set of transcription factors. The MEF2 family plays a critical role in these processes.
Publication Title
Antagonistic regulation of cell-cycle and differentiation gene programs in neonatal cardiomyocytes by homologous MEF2 transcription factors.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
AF10 regulates progressive H3K79 methylation and HOX gene expression in diverse AML subtypes.
Sample Metadata Fields
Specimen part, Disease
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Gene expression data from VHL teratomas comparing genes differentially expressed based on apoptotic response to tumor microenvironment.
Publication Title
Pleiotropic effects of the trichloroethylene-associated P81S VHL mutation on metabolism, apoptosis, and ATM-mediated DNA damage response.
Sample Metadata Fields
Specimen part
View Samples
GSE8438- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In human cells, Staufen1 is double-stranded RNA-binding protein involved in several cellular functions including mRNA localization, translation and decay. We used a genome wide approach to identify and compare the mRNA targets of mammalian Staufen1. The mRNA content of Staufen1 mRNPs was identified by probing DNA microarrays with probes derived from mRNAs isolated from immunopurified Staufen-containing complexes following transfection of HEK293T cells with a Stau1-HA expressor. Our results indicate that 7% of the cellular RNAs expressed in HEK293T cells are found in Stau1-containing mRNPs. There is a predominance of mRNAs involved in cell metabolism, transport, transcription, regulation of cell processes and catalytic activity.
Publication Title
A genome-wide approach identifies distinct but overlapping subsets of cellular mRNAs associated with Staufen1- and Staufen2-containing ribonucleoprotein complexes.
Sample Metadata Fields
No sample metadata fields
View Samples GSE8437- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In human cells, Staufen2 is a double-stranded RNA-binding protein involved in several cellular functions. Although 51% identical to Staufen1, these proteins are nevertheless found in different RNA particles. In addition, differential splicing events generate Staufen2 isoforms that only differ at their N-terminal extremities. We used a genome wide approach to identify and compare the mRNA targets of mammalian Staufen2 isoforms. The mRNA content of Staufen mRNPs was identified by probing DNA microarrays with probes derived from mRNAs isolated from immunopurified Staufen2-containing complexes following transfection of HEK293T cells with Stau2-HA (59kDa) or Stau2-HA (62kDa) expressors. Our results indicate that 11% of the cellular RNAs expressed in HEK293T cells are found in Stau2-containing mRNPs. There is a predominance of mRNAs involved in cell metabolism, transport, transcription, regulation of cell processes and catalytic activity.
Publication Title
A genome-wide approach identifies distinct but overlapping subsets of cellular mRNAs associated with Staufen1- and Staufen2-containing ribonucleoprotein complexes.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
To better understand the scale of gene expression changes that occur during the formation of mature adipocytes from preadipocytes, we compared and characterised the transcriptome profile of mesenchymal stromal cells derived from human adipose tissue, otherwise known as adipose-derived stromal cells (ASCs), undergoing adipocyte differentiation on day 1, 7, 14 and 21 (representing the early to late stage process of adipogenesis). Microarray technique was systematically employed to study gene expression in adipose-derived stromal cells during adipogenic differentiation over a 21 day period to identify genes that are important in driving adipogenesis in humans.
Publication Title
Genome-wide analysis of gene expression during adipogenesis in human adipose-derived stromal cells reveals novel patterns of gene expression during adipocyte differentiation.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples