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SRP194327
Drosophila melanogaster
73 Downloadable Samples
Illumina HiSeq 2500
Description
Ageing populations pose one of the main public health crises of our time. Reprogramming gene expression by altering the activities of sequence-specific transcription factors (TF) can ameliorate deleterious effects of age. Here we explore how a circuit of TFs coordinates pro-longevity transcriptional outcomes, which reveals a multi-tissue and multi-species role for an entire protein family: the E-twenty-six (ETS) TFs. In Drosophila, reduced insulin/IGF signalling (IIS) extends lifespan by coordinating activation of Aop, an ETS transcriptional repressor, and Foxo, a Forkhead transcriptional activator. Aop and Foxo bind the same genomic loci, and we show that, individually, they effect similar transcriptional programmes in vivo. In combination, Aop can both moderate or synergise with Foxo, dependent on promoter context. Moreover, Foxo and Aop oppose the activities of Pnt, an ETS transcriptional activator, effecting a transcriptomic programme that correlates lifespan outcomes. Directly limiting Pnt extended lifespan, suggesting this is how Aop and Foxo promote longevity. The lifespan-limiting role of Pnt appears to be balanced by a requirement for metabolic regulation in young flies, in which the Aop-Pnt-Foxo circuit determines nutrient storage, and Pnt regulates lipolysis and responses to nutrient stress. Molecular functions are conserved amongst ETS TFs, suggesting others may also affect ageing. We show that Ets21C limits lifespan, functioning in the same genetic network as Foxo and IIS. Other ETS TFs appear to play roles in fly ageing in multiple contexts, since inhibiting the majority of the family in intestine, adipose or neurons extended lifespan. We expand the repertoire of lifespan-limiting ETS TFs in C. elegans, confirming their conserved function in ageing. Altogether this study reveals that roles of ETS TFs in physiology and lifespan are conserved throughout the family, both within and between species. Overall design: foxo, aopACT and pntP1 overexpression in S106 D. melanogaster, polyA RNAseq.
Publication Title
Longevity is determined by ETS transcription factors in multiple tissues and diverse species.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We report here senescent changes in the structure and organization of the mucociliary pseudostratified epithelium of the mouse trachea and the main stem bronchi. We confirm previous reports of the graduate appearance of age-related, gland-like structures (ARGLS) in the submucosa, espeically in the intercartilage regions and carina. Immunohistochemistry shows these structures contain ciliated and secretory cells and Krt5+ basal cells, but not the myoepithelial cells or ciliated ducts typical of normal submucosal glands. Data suggests they arise de novo by budding from teh surface epithelium rather than by delayted growth of small or cryptic submucosal glands. In old mice the surface epithelium contains fewer cells per unit length than in young mice and the proportion of Krt5+, p63+ basal cells is reduced in both males and females. However, there appears to be no significant difference in the ability of basal stem cells isolated from individual young and old mice to form clonal tracheospheres in culture or in the ability of the pithelium to repair after damage by inhaled sulfur dioxide. Gene expression analysis by Affymetrix microarray and quantitative PCR, as well as immunohistochemistry and flow sorting studies, are consistent with low-grade chronic inflammation in the tracheas of old versus young mice. The significance of these changes for ARGL formation are not clear since several treatments that induce acute inflammation in young mice did not result in budding of the surface epithelium.
Publication Title
Age-related changes in the cellular composition and epithelial organization of the mouse trachea.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The conducting airway epithelium of the rodent and human lung is made up of about equal proportions of ciliated and secretory cells. In addition, in regions where the epithelium is pseudostratfied, ~30% of the epithelium consists of undifferentiated basal cells (BCs). Evidence suggests that these BCs are multipotent stem cells that can self renew over the long term and give rise to both ciliated and secretory lineages. The goal of this project is to identify cellular and molecular mechanisms by which the basal cells normally maintain the epithelium and repair it after injury.
Publication Title
BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The conducting airway epithelium of the rodent and human lung is underlaid by mesenchymal cells that include vasculature, smooth muscle, fibroblasts and cartilage. The goal of this project is to identify cellular and molecular changes in the mesenchyme after injury to the epithelium by exposure to SO2 and which may participate in repair of the epithelium
Publication Title
BMP signaling and cellular dynamics during regeneration of airway epithelium from basal progenitors.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We identified DCIR2+DCs but not DEC205+DCs as able to induce peripheral T cell tolerance in pre-diabetic autoimmune NOD mice. To determine what distinct genetic programs are elicited in the auto-reactive CD4 T cells early after stimulation by these two DC subsets, we utilized adoptive transfer of BDC2.5 CD4 T cells into NOD mice, which were then given chimeric antibody to deliver the beta-cell specific antigen to either DCIR2+DCs or DEC205+DCs, leading to BDC2.5 CD4 T cell specific stimulation in vivo. The analysis shows that the negative transcriptional factor Zbtb32 (ROG) is up-regulated more in BDC2.5 CD4 T cells after stimulated with a antigen via DCIR2+DCs presentation, compared with DEC205+DCs, suggesting the involvement of Zbtb32 in DCIR2+DCs-mediated auto-reactive T cell tolerance in disease ongoing NOD mice.
Publication Title
DCIR2+ cDC2 DCs and Zbtb32 Restore CD4+ T-Cell Tolerance and Inhibit Diabetes.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
We investigated the global gene expression changes in normal and Brg1-deleted mesoderm differentiation of mouse embryonic stem cells. Overall design: RNAseq analysis of poly-adenylated RNA levels for 3 conditions: Day2 of differentiation, Day4 THF (Control), and Day4 4OHT (Brg1-deleted). 2 replicates per condition.
Publication Title
Brg1 modulates enhancer activation in mesoderm lineage commitment.
Sample Metadata Fields
Cell line, Subject, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Obesity-associated metabolic complications are generally considered to emerge from abnormalities in carbohydrate and lipid metabolism, whereas the status of protein metabolism is not well studied. Here, we performed comparative polysome and associated transcriptional profiling analyses to study the dynamics and functional implications of endoplasmic reticulum (ER)-associated protein synthesis in the mouse liver under conditions of obesity and nutrient deprivation.
Publication Title
Polysome profiling in liver identifies dynamic regulation of endoplasmic reticulum translatome by obesity and fasting.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
Gene expression variation upon folate deficiency and repletion in human foreskin keratinocytes immortalized by HPV16E6E7 Overall design: Effects of folate modulation on several cellular events such as DNA stability
Publication Title
Folate Repletion after Deficiency Induces Irreversible Genomic and Transcriptional Changes in Human Papillomavirus Type 16 (HPV16)-Immortalized Human Keratinocytes.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 70 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Our aim is to identify circadian transcripts that are co-regulated with [Ca2+]cyt, with the eventual goal of identifying genetic regulators and targets for circadian oscillations of [Ca2+]cyt. We have identified two conditions in which [Ca2+]cyt behaves differently to other circadian outputs. 1. Treatment of plants with nicotinamide, a metabolic inhibitor of ADPR cyclase, abolishes the circadian oscillations of [Ca 2+]cyt. However, leaf movement, CCA1, LHY, TOC1 and CAB transcript abundance and CAB promoter activity are all rhythmic albeit with a longer period (Dodd et al., 2007). 2. The toc1-1 mutant, which shortens the circadian period of all other rhythms tested, has no effect on the period of [Ca2+]cyt oscillations (Xu et al., 2007). We will measure the circadian regulation of transcript abundance in wild type (C24), toc1-1 and nicotinamide (C24)-treated plants.
Publication Title
Correct biological timing in Arabidopsis requires multiple light-signaling pathways.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples