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SRP064298
Mus musculus
597 Downloadable Samples
Illumina HiSeq 2500
Description
Diurnal oscillations of gene expression are a hallmark of rhythmic physiology across most living organisms. Such oscillations are controlled by the interplay between the circadian clock and feeding rhythms. While rhythmic mRNA accumulation has been extensively studied, comparatively less is known about their transcription and translation. Here, we quantified simultaneously temporal transcription, accumulation, and translation of mouse liver mRNAs under physiological light-dark conditions and ad libitum or night-restricted feeding in wild-type and Bmal1 deficient animals. We found that rhythmic transcription predominantly drives rhythmic mRNA accumulation and translation for a majority of genes. Comparison of wild-type and Bmal1 KO mice shows that circadian clock and feeding rhythms have broad impact on rhythmic genes expression, Bmal1 deletion having surprisingly more impact at the post-transcriptional level. Translation efficiency is differentially regulated during the diurnal cycle for genes with 5'-TOP sequences and for genes involved in mitochondrial activity and harboring a TISU motif. The increased translation efficiency of 5'-TOP and TISU genes is mainly driven by feeding rhythms but Bmal1 deletion impacts also amplitude and phase of translation, including TISU genes. Together this study emphasizes the complex interconnections between circadian and feeding rhythms at several steps ultimately determining rhythmic gene expression and translation. Overall design: RNA-Seq from total RNA of mouse liver during the dirunal cycle. Time-series mRNA profiles of wild type (WT) and Bmal -/- mice under ad libitum and night restriced feeding regimen were generated by deep sequencing.
Publication Title
Diurnal Oscillations in Liver Mass and Cell Size Accompany Ribosome Assembly Cycles.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 50 Downloadable Samples
- Illumina HiSeq 2500
Description
Mammalian gene expression displays widespread circadian oscillations. Rhythmic transcription underlies the core clock mechanism, but it cannot explain numerous observations made at the level of protein rhythmicity. We have used ribosome profiling in mouse liver to measure the translation of mRNAs into protein around-the-clock and at high temporal and nucleotide resolution. Transcriptome-wide, we discovered extensive rhythms in ribosome occupancy, and identified a core set of ˜150 mRNAs subject to particularly robust daily changes in translation efficiency. Cycling proteins produced from non-oscillating transcripts revealed thus far unknown rhythmic regulation associated with specific pathways (notably in iron metabolism, through the rhythmic translation of transcripts containing iron responsive elements), and indicated feedback to the rhythmic transcriptome through novel rhythmic transcription factors. Moreover, estimates of relative levels of core clock protein biosynthesis that we deduced from the data explained known features of the circadian clock better than did mRNA expression alone. Finally, we identified uORF translation as a novel regulatory mechanism within the clock circuitry. Consistent with the occurrence of translated uORFs in several core clock transcripts, loss-of-function of Denr, a known regulator of re-initiation after uORF usage and of ribosome recycling, led to circadian period shortening in cells. In summary, our data offer a framework for understanding the dynamics of translational regulation, circadian gene expression, and metabolic control in a solid mammalian organ. Overall design: A total of 48 mice were entrained under 12hours light:dark conditions for 2 weeks and also collected under 12hours light:dark. Mice were sacrificed every two hours during the 24 hours daily cycle. Two replicates per time point, each replicate is a pool of 2 livers.
Publication Title
Diurnal Oscillations in Liver Mass and Cell Size Accompany Ribosome Assembly Cycles.
Sample Metadata Fields
No sample metadata fields
View Samples- Xenopus laevis
- 5 Downloadable Samples
Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
Analysis of epithelial explants injected with the intracellular domain of Notch (ICD) to block the formation of multi-ciliate and proton secreting cells or with dominant negative human Mastermind (HMM) to induce the formation of ectopic multi-ciliate and proton secreting cells. Results show which genes are up or down-regulated when HMM is compared to ICD.
Publication Title
Specification of ion transport cells in the Xenopus larval skin.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Xenopus laevis
- 4 Downloadable Samples
- Affymetrix Xenopus laevis Genome 2.0 Array (xlaevis2)
Description
Analysis of epithelial explants injected with the intracellular domain of Notch (ICD) to block the formation of multi-ciliate and proton secreting cells or with dominant negative human Mastermind (HMM) or a DNA binding mutant of Mastermind (DBM) to induce the formation of ectopic multi-ciliate and proton secreting cells. Results show which genes are up or down-regulated when DBM/HMM are compared to ICD.
Publication Title
Multicilin promotes centriole assembly and ciliogenesis during multiciliate cell differentiation.
Sample Metadata Fields
No sample metadata fields
View Samples- Xenopus laevis
- 5 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
Analysis of epithelial explants injected with the intracellular domain of Notch (ICD) to block the formation of multi-ciliate cells, either alone or along with FoxJ1. FoxJ1 misexpression leads to the induction fo ectopic cilia in Xenopus laevis epithelia. Results show which genes are affected by FoxJ1 during the induction of ectopic cilia.
Publication Title
The forkhead protein Foxj1 specifies node-like cilia in Xenopus and zebrafish embryos.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 54 Downloadable Samples
- Illumina HiSeq 2500
Description
Short-term bed rest is used to simulate muscle disuse in humans. In our previous reports, we found that 5d of bed rest induced a ~4% loss of skeletal muscle mass in OLD (60-79 y) but not YOUNG (18-28 y) subjects. Identifying muscle transcriptional events in response to bed rest and age-related differences will help identify therapeutic targets to offset muscle loss in vulnerable older adult populations. Skeletal muscle dysregulation during bed rest in the old may be driven by alterations in molecules related to fibrosis, inflammation, and cell adhesion. This information may aide in the development of mechanistic-based therapies to combat muscle atrophy during short-term disuse. Short-term muscle disuse is also characterized by skeletal muscle insulin resistance, though this response is divergent across subjects. The mechanisms regulating inactivity-induced insulin resistance between populations that are more or less susceptible to disuse-induced insulin resistance are not known, and delineated by age. High Susceptibility participants were uniquely characterized with muscle gene responses described by a decrease in pathways responsible for lipid uptake and oxidation, decreased capacity for triglyceride export (APOB), increased lipogenesis (i.e., PFKFB3, FASN), and increased amino acid export (SLC43A1). Overall design: RNA was isolated and sequenced from muscle biopsies obtained from the vastus lateralis of YOUNG (N=9) and OLD (N=18) men and women before and after five days of bed rest. Sequencing libraries (18 pM) were chemically denatured and applied to an Illumina TruSeq v3 single read flowcell using an Illumina cBot. Hybridized molecules were clonally amplified and annealed to sequencing primers with reagents from an Illumina TruSeq SR Cluster Kit v3-cBot-HS (GD-401-3001). Following transfer of the flowcell to an Illumina HiSeq 2500 instrument (HCS v2.0.12 and RTA v1.17.21.3), a 50 cycle single read sequence run was performed using TruSeq SBS v3 sequencing reagents (FC-401-3002). The design formula was constructed by following the section on group-specific condition effects, individuals nested within groups in the DESeq2 vignette. The design included age + age:nested + age:time to test for differences in bed rest in old subjects, young subjects and the interaction, in this case if bed rest effects are different between the two age groups (where age is young or old, nested is patient number nested by age and time is pre- or post-bed rest). A similar design was used to determine susceptibility to disuse-induced insulin resistance, where “susceptibility” took the place of “age”.
Publication Title
Disuse-induced insulin resistance susceptibility coincides with a dysregulated skeletal muscle metabolic transcriptome.
Sample Metadata Fields
Sex, Specimen part, Subject, Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
gene expression at 6h of differentiation of Human endometrial stromal cell expressing either or both of PRA and PRB
Publication Title
Roles of progesterone receptor A and B isoforms during human endometrial decidualization.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
The T-box transcription factor TBX18 is essential to mesenchymal cell differentiation in several tissues and Tbx18 loss-of-function results in dramatic organ malformations and perinatal lethality. Here we demonstrate for the first time that Tbx18 is required for the normal development of periductal smooth muscle stromal cells in prostate, particularly in the anterior lobe, with a clear impact on prostate health in adult mice. Prostate abnormalities are only subtly apparent in Tbx18 mutants at birth; to examine postnatal prostate development we utilized a relatively long-lived hypomorphic mutant and a novel conditional Tbx18 allele. Similar to the ureter, cells that fail to express Tbx18 do not condense normally into smooth muscle cells of the periductal prostatic stroma. However, in contrast to ureter, the periductal stromal cells in mutant prostate assume a hypertrophic, myofibroblastic state and the adjacent epithelium becomes grossly disorganized. To identify molecular events preceding the onset of this pathology, we compared gene expression in the urogenital sinus (UGS), from which the prostate develops, in Tbx18-null and wild type littermates at two embryonic stages. Genes that regulate cell proliferation, smooth muscle differentiation, prostate epithelium development, and inflammatory response were significantly dysregulated in the mutant urogenital sinus around the time that Tbx18 is first expressed in the wild type UGS, suggesting a direct role in regulating those genes. Together, these results argue that Tbx18 is essential to the differentiation and maintenance of the prostate periurethral mesenchyme and that it indirectly regulates epithelial differentiation through control of stromal-epithelial signaling. Overall design: Embryos were collected from timed matings of Tbx18Gfp/+ knock-in mutants at E16.5 and E18.5, and genotyped to identify Tbx18Gfp/Gfp null mutants and wild-type (WT) littermates. The urogenital sinus (UGS) was dissected and used to extract RNA from each of three animals of each genotype. The RNA samples were pooled to generate libraries for sequencing.
Publication Title
Tbx18 Regulates the Differentiation of Periductal Smooth Muscle Stroma and the Maintenance of Epithelial Integrity in the Prostate.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2000
Description
A GFP-expressing recombinant A/Puerto Rico/8/1934 influenza virus was used to infect C57BL/6 wild type mice and on day 3 post infection, lung alveolar epithelial cells (AEC) were isolated and sorted based on GFP expression. GFP+ AEC represent the infected AEC and GFP- AEC represent the bystander AEC. AEC were also sorted from uninfected mice to serve as controls. Overall design: AEC from infected mice were pooled to make three (3) infected GFP+ AEC replicates for sequencing. Five (5) bystander GFP- replicates and five (5) uninfected AEC replicates were also isolated for sequencing
Publication Title
Transcriptome Analysis of Infected and Bystander Type 2 Alveolar Epithelial Cells during Influenza A Virus Infection Reveals <i>In Vivo</i> Wnt Pathway Downregulation.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Mus musculus
- 134 Downloadable Samples
- Illumina HiSeq 2500
Description
Profound changes in cancer cell identity can alter malignant potential and therapeutic response. Loss of the pulmonary lineage specifier NKX2-1 augments the growth of KRAS-driven lung adenocarcinoma and causes pulmonary to gastric transdifferentiation. Here we show that the transcription factors FoxA1 and FoxA2 are required for initiation of mucinous NKX2-1-negative lung adenocarcinomas in the mouse and for activation of their gastric differentiation program. Foxa1/2 deletion severely impairs tumor initiation and causes a proximal shift in cellular identity, yielding tumors expressing markers of the squamocolumnar junction of the gastrointestinal tract. In contrast, stochastic loss of FoxA1/2 expression in NKX2-1-negative tumors is associated with keratinizing squamous differentiation. Using sequential in vivo recombination, we find that FoxA1/2 loss in established KRAS-driven neoplasia is sufficient for direct induction of keratinizing squamous cell carcinomas in the lung. Thus, NKX2-1, FoxA1 and FoxA2 coordinately regulate the growth and identity of lung adenocarcinoma in a context-specific manner. Overall design: Murine lung tumor cells of differing genotypes were isolated by FACS and subjected to single cell analysis using the Fluidigm C1 platform.
Publication Title
FoxA1 and FoxA2 drive gastric differentiation and suppress squamous identity in NKX2-1-negative lung cancer.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples