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GSE53503
Mus musculus
4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
YY1 is indispensable for Lgr5+ intestinal stem cell renewal.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Crypts were isolated from either control or YY1f/f; Vil-Cre-ERT2 mice treated with tamoxifen for 4 days to induce knockout
Publication Title
YY1 is indispensable for Lgr5+ intestinal stem cell renewal.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
During late gestation, structures called villi extend into the intestinal lumen to dramatically increase the surface area of the intestinal epithelium, preparing the gut for the neonatal diet. Incomplete development of the intestine is the most common gastrointestinal complication in neonates, but the causes are unclear. We provide evidence that Yin-Yang1 (Yy1) is critical for intestinal villus development. YY1 loss in the developing endoderm had no apparent consequences until late gestation, after which the intestine differentiated poorly and exhibited severely stunted villi. Transcriptome analysis revealed that YY1 is required for mitochondrial gene expression, and ultrastructural analysis confirmed compromised mitochondrial integrity in the mutant intestine. We found increased oxidative phosphorylation gene expression at the onset of villus elongation, suggesting that aerobic respiration may function as a regulator of villus growth. Mitochondrial inhibitors blocked villus growth in a fashion similar to Yy1 loss, thus further linking oxidative phosphorylation with late-gestation intestinal development. Interestingly, we find necrotizing enterocolitis patients also exhibit decreased expression of oxidative phosphorylation genes. Our study highlights the still unappreciated role of metabolic regulation during organogenesis, and suggests it may contribute to neonatal gastrointestinal disorders.
Publication Title
A YY1-dependent increase in aerobic metabolism is indispensable for intestinal organogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
Illumina HiSeq 2500
Description
In the current work, we add to the understanding of differentiated-cell-derived tumorigenesis by demonstrating that simultaneous loss of SMAD4 and activation of the WNT pathway triggers stem cell properties and adenoma formation in the differentiated epithelium. Under normal conditions, SMAD4 loss does not immediately affect the normal tissue homeostasis in the intestine. However, after approximately 6 months, adenomas will develop and feature elevated WNT signaling, suggesting that SMAD4 loss predisposes to WNT-driven tumors. Interestingly, ectopic elevation of WNT in the context of a SMAD4 mutant background triggers stem cell activity and adenoma formation in the differentiated epithelium. Thus Smad4 functions to suppress villus cells from re-entering the cell cycle and functioning as stem cells upon exposure to high levels of WNT. Thus, we report a new mechanism through which differentiated cells can contribute to tumor formation. Overall design: RNAs were extracted from crypt jejunal epithelia of the indicated genotypes (Smad4f/f;Villin-CreER(T2) and Smad4f/f; Ex3f/+;Villin-CreER(T2)) in triplicates, one day following 4 consecutive days of tamoxifen injection. Uninjected mice served as control. After flushing the freshly harvested jejunum with cold PBS, the epithelia was dissociated from underlying mesenchyme by incubating with 3 mM EDTA/PBS at 4°C as described previously (Perekatt, 2014), and filtered through 70 micron filter to isolate the crypts. The crypts were washed with PBS, and pelleted to remove excess PBS prior to addition of TRIzol for RNA extraction according to manufacturer's protocols.
Publication Title
SMAD4 Suppresses WNT-Driven Dedifferentiation and Oncogenesis in the Differentiated Gut Epithelium.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Double-stranded RNA-binding proteins are key elements in the intracellular localization of mRNA and its local translation. Staufen is a double-stranded RNA binding protein involved in the localised translation of specific mRNAs during Drosophila early development and neuronal cell fate. The human homologue Staufen1 forms RNA-containing complexes that include proteins involved in translation and motor proteins to allow their movement within the cell, but the mechanism underlying translation repression in these complexes is poorly understood. Here we show that human Staufen1-containing complexes contain essential elements of the gene silencing apparatus, like Ago1-3 proteins, and we describe a set of miRNAs specifically associated to complexes containing human Staufen1. Among these, miR124 stands out as particularly relevant because it appears enriched in human Staufen1 complexes and is over-expressed upon differentiation of human neuroblastoma cells in vitro. In agreement with these findings, we show that expression of human Staufen1 is essential for proper dendritic arborisation during neuroblastoma cell differentiation, yet it is not necessary for maintenance of the differentiated state, and suggest potential human Staufen1 mRNA targets involved in this process.
Publication Title
Human Staufen1 associates to miRNAs involved in neuronal cell differentiation and is required for correct dendritic formation.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 29 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This study is part of previous epidemiologic project, including a population-based survey (Sao Paulo Ageing & Health study (SPAH Study). The data from this study was collected between 2015 to 2016 and involved elderly women (ages ≥65 yeas) living in the Butanta district, Sao Paulo. The purpose of the study was identification of association between transcriptome and the osteo metabolism diseases phenotype, like osteoporosis, vertebral fracture and coronary calcification.
Publication Title
Overexpression of SNTG2, TRAF3IP2, and ITGA6 transcripts is associated with osteoporotic vertebral fracture in elderly women from community.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 17 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Despite the well-established role of the frontal and posterior peri-sylvian cortices in many facets of human-cognitive specializations, including language, little is known about the developmental patterning of these regions in human brain. We performed a genome-wide analysis of human cerebral patterning during mid-gestation, a critical epoch in cortical regionalization. A total of 345 genes were identified as differentially expressed (DE) between superior temporal gyrus (STG) and the remaining cerebral cortex (CTX). GO categories representing transcription factors were enriched in STG, while cell-adhesion and extracellular matrix molecules, were enriched in the other cortical regions. Q-PCR or in situ hybridization were performed to validate differential expression in a subset of 32 genes, most of which were confirmed. LIM domain binding 1 (LDB1), which we show to be enriched in the STG, is a recently identified interactor of LIM domain only 4 (LMO4), a gene known to be involved in the asymmetric pattering of the peri-sylvian region in the developing human brain. Protocadherin 17 (PCDH17), a neuronal cell adhesion molecule, was highly enriched in focal regions of the human prefrontal cortex. Contactin Associated Protein-Like 2 (CNTNAP2), in which mutations are known to cause autism, epilepsy and language delay, showed a remarkable pattern of anterior enriched expression in cortical regions important for human higher cognition. Importantly, a similar pattern was not observed in the mouse or rat. These data highlight the importance of expression analysis of human brain and the utility of cross-species comparisons of gene expression. Genes identified here provide a foundation for understanding molecular aspects of human-cognitive specializations and disorders that disrupt them.
Publication Title
Genome-wide analyses of human perisylvian cerebral cortical patterning.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Protein synthesis belongs to the most energy consuming processes in the cell. Lowering oxygen tension below normal (hypoxia) causes a rapid inhibition of global mRNA translation due to the decreased availability of energy. Interestingly, subsets of mRNAs pursue active translation under such circumstances. In human fibrosarcoma cells (HT1080) exposed to prolonged hypoxia (36 h, 1% oxygen) we observed that transcripts are either increasingly or decreasingly associated with ribosomes localized at the endoplasmic reticulum (ER). In a global setting it turned out that only 31% of transcripts showing elevated total-RNA levels were also increasingly present at the ER in hypoxia. These genes, regulated by its expression as well as its ER-localization, belong to the gene ontologys hypoxia response, glycolysis and HIF-1 transcription factor network supporting the view of active mRNA translation at the ER during hypoxia. Interestingly, a large group of RNAs was found to be unchanged at the expression level, but translocate to the ER in hypoxia. Among these are transcripts encoding translation factors and >180 ncRNAs. In summary, we provide evidence that protein synthesis is favoured at the ER and, thus, partitioning of the transcriptome between cytoplasmic and ER associated ribosomes mediates adaptation of gene expression in hypoxia.
Publication Title
Hypoxia-induced gene expression results from selective mRNA partitioning to the endoplasmic reticulum.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mitogen activated protein kinase (MAPK) signaling regulates differentiation of many cell types. During myogenesis in particular, p38a MAPK (MAPK14) phosphorylates multiple transcriptional regulators to modulate muscle-specific gene expression. Among the p38a MAPK modulated genes is the muscle-specific transcriptional regulator Myogenin (Myog) that is also essential to complete the muscle differentiation program, and while it is known that both p38a MAPK and Myog are critically required for myogenesis, the individual contribution of each of these proteins is poorly defined. Here we show that Myog expression (in the absence of p38a MAPK signaling) is sufficient to establish expression of many late markers of muscle differentiation and to mediate cell migration. However, Myog expression alone did not led to the formation of multinucleated muscle cells, highlighting a critical role for p38a MAPK in myoblast fusion. Using comparative microarray analysis we identified p38a MAPK-dependent genes that are not regulated by Myog
Publication Title
Comparative expression profiling identifies differential roles for Myogenin and p38α MAPK signaling in myogenesis.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
E2 exposure significantly decreased peak viral titer in hNECs from female donors. We used microarray analyses to identify global gene expression patterns between E2 and vehicle exposed hNECs from female donors
Publication Title
Estrogenic compounds reduce influenza A virus replication in primary human nasal epithelial cells derived from female, but not male, donors.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples