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GSE35682
Mus musculus
25 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Loss of Notch1 in retinal progenitor cells (RPCs) during postnatal retinal development results in the overproduction of rod photoreceptors at the expense of interneurons and glia. To examine the molecular underpinnings of this observation, microarray analysis of singla retinal cells from wildtype (WT) or Notch1 conditional knockout (N1-CKO) retinas was performed. The majority of N1-CKO cells lost expression of known Notch target genes. These cells also had low levels of RPC and cell cycle genes, and robustly upregulated rod precursor genes. In addition, single WT cells, in which cell cycle marker genes were downregulated, expressed markers of both rod photoreceptors and interneurons. These results demonstrate that individual, newly postmitotic retinal cells can begin to differentiate into more than one cell type, and that this transitional state may be dependent on Notch1 signaling.
Publication Title
Notch1 is required in newly postmitotic cells to inhibit the rod photoreceptor fate.
Sample Metadata Fields
Specimen part
View Samples- Saccharomyces cerevisiae
- 4 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Rsp5 is an essential and multi-functional E3 ubiquitin ligase in Saccharomyces cerevisiae. We previously isolated the Ala401Glu rsp5 mutant, which is hypersensitive to various stresses. To understand the function of Rsp5 in stress responses, suppressor genes whose overexpression allows rsp5A401E cells to grow at high temperature were screened. The KIN28 and POG1 genes, encoding a subunit of the transcription factor TFIIH and a putative transcriptional activator, respectively, were identified as multicopy suppressors of not only high temperature but also LiCl stresses. The overexpression of Kin28 and Pog1 in rsp5A401E cells caused an increase in the transcriptional level of some stress proteins when exposed to temperature up-shift. DNA microarray analysis under LiCl stress revealed that the transcriptional level of some proteasome components was increased in rsp5A401E cells overexpressing Kin28 or Pog1. These results suggest that the overexpression of Kin28 and Pog1 enhances the protein refolding and degradation pathways in rsp5A401E cells.
Publication Title
Overexpression of two transcriptional factors, Kin28 and Pog1, suppresses the stress sensitivity caused by the rsp5 mutation in Saccharomyces cerevisiae.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 39 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Sustained caloric restriction (CR) extends lifespan in animal models but the mechanism and primary tissue target(s) have not been identified. Gene expression changes with aging and CR were examined in both heart and subcutaneous white adipose tissue (WAT) of F344 male rats using Affymetrix RAE 230 arrays and validated by qRT-PCR on 18 genes. In heart, age- associated changes but not CR-associated changes in old. In WAT, genes were identified where the aging change is suppressed by CR (candidate markers of healthy aging) and those affected by CR but not normal aging (candidate longevity assurance genes). 10-21% of age-associated genes were regulated in common between tissues. Gene set enrichment analysis (GSEA) revealed coordinate small magnitude changes in ribosomal, proteasomal, and mitochondrial genes with similarities between heart and WAT. Further analysis revealed PPARgamma as a potential upstream regulator of altered gene expression in old CR WAT. These results demonstrate a reduced mRNA response to CR with age in heart relative to WAT. In WAT, we identified candidate CR mimetic targets and candidate markers of healthy aging. These data suggest a role for subcutaneous WAT in the effects of CR and strengthen the role for PPAR signaling in aging and CR while indicating that the effects of CR in heart can occur independent of global changes in mRNA level.
Publication Title
Transcriptional response to aging and caloric restriction in heart and adipose tissue.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
An Ancient Fecundability-Associated Polymorphism Creates a GATA2 Binding Site in a Distal Enhancer of HLA-F.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The RSK2 gene is responsible for Coffin-Lowry syndrome, an X-linked monogenic disease associating severe learning deficit andassociated to typical facial and digital abnormalities and skeletal changes. Craniofacial and dental anomalies encountered in this rare disease have been poorly characterized.
Publication Title
RSK2 is a modulator of craniofacial development.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 4 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Adult neurogenesis occurs in mammals and provides a mechanism for continuous neural plasticity in the brain.However, little is known about the molecular mechanisms regulating hippocampal neural progenitor cells (NPCs) and whether their fate can be pharmacologically modulated to improve neural plasticity and regeneration. Here, we report the characterization of a unique small molecule (KHS101) that selectively induces a neuronal differentiation phenotype. Mechanism of action studies revealed a link of KHS101 to cell cycle exit and specific binding to the TACC3 protein, whose knockdown in NPCs recapitulates the KHS101-induced phenotype. Upon systemic administration, KHS101 distributed to the brainandresulted in a significant increase in neuronal differentiation in vivo. Our findings indicate that KHS101 accelerates neuronal differentiation by interaction with TACC3 and may provide a basis for pharmacological intervention.directed at endogenous NPCs.
Publication Title
A small molecule accelerates neuronal differentiation in the adult rat.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Research resource: Genome-wide profiling of progesterone receptor binding in the mouse uterus.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Progesterone (P4) signaling through its nuclear transcription factor, the progesterone receptor (PR), is essential for normal uterine function. Although deregulation of PR mediated signaling is known to underscore uterine dysfunction and a number of endometrial pathologies, the early molecular mechanisms of this deregulation are unclear. To address this issue, we have defined the genome-wide PR and GATA2 cistrome in the murine uterus using chromatin immunoprecipitation followed by massively parallel sequencing (ChIP-seq). In uteri of ovariectomized mice, we identified 6367 PR binding sites in the absence of P4 ligand; however, this number increased at nearly three fold (18,432) following acute P4 exposure. Sequence analysis revealed that approximately 73% of these binding sites contain a progesterone response element (PRE) or a half-site motif recognized by the PR. Many previously identified P4 target genes known to regulate uterine function were found to contain PR binding sites, confirming the validity of our methodology. In addition we identified 46,183 GATA2 binding sites in P4 treatment conditions with 7,954 binding sites overlapping that of the PR.
Publication Title
Research resource: Genome-wide profiling of progesterone receptor binding in the mouse uterus.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Although mutations in Kras are present in 21% of lung tumors, there is a high level of heterogeneity in phenotype and outcomes amongst lung cancer patients suggesting the importance of other pathways. Wnt/-catenin signaling is a known oncogenic pathway that plays a well defined role in colon and skin cancer but its role in lung cancer remains unclear. We show that activation of Wnt/-catenin in the bronchiolar epithelium of the adult lung does not promote tumor development by itself. However, activation of Wnt/- catenin signaling leads to a dramatic increase in tumor formation both in overall tumor number and size compared to KrasG12D alone. We show that activation of Wnt/- catenin signaling significantly alters the KrasG12D tumor phenotype resulting in a phenotypic switch from bronchiolar epithelium to the highly proliferative distal progenitors found in the embryonic lung. This is associated with a decrease in E- cadherin expression at the cell surface which may increase metastasis in Wnt/-catenin signaling positive tumors. Together, these data suggest that activation of Wnt/-catenin signaling in combination with other oncogenic pathways in lung epithelium may lead to a more aggressive phenotype due to the imposition of an embryonic distal progenitor phenotype accompanied by decreased E-cadherin expression.
Publication Title
Wnt/β-catenin signaling accelerates mouse lung tumorigenesis by imposing an embryonic distal progenitor phenotype on lung epithelium.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Foxp1/4 transcription factors are conserved transcriptional repressors expressed in overlapping patterns during lung development as well as in the adult lung. However, the role of Foxp1/4 in development and homeostasis of the pseudostratified epithelium of the proximal airways and trachea is unknown.
Publication Title
Foxp1/4 control epithelial cell fate during lung development and regeneration through regulation of anterior gradient 2.
Sample Metadata Fields
Specimen part
View Samples