This SuperSeries is composed of the SubSeries listed below.
Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Specimen part
View SamplesSox9 is a transcription factor expressed in most solid tumors. However, the molecular mechanisms underlying Sox9 function during tumorigenesis remain unclear. Here, using a genetic mouse model of basal cell carcinoma (BCC), the most frequent cancer in human, we show that Sox9 is expressed from the earliest step of tumor formation in a Wnt/-catenin dependent manner. Deletion of Sox9 together with the constitutive activation of Hedgehog (HH) signaling completely prevents BCC formation and leads to a progressive loss of oncogene expressing cells. Transcriptional profiling of oncogene expressing cells with Sox9 deletion, combined with in vivo ChIP-sequencing uncovers a cancer-specific gene network regulated by Sox9 that promotes stemness, extracellular matrix (ECM) deposition and cytoskeleton remodeling while repressing epidermal differentiation. Our study identifies the molecular mechanisms regulated by Sox9 that links tumor initiation and invasion.
Sox9 Controls Self-Renewal of Oncogene Targeted Cells and Links Tumor Initiation and Invasion.
Specimen part
View SamplesStudy the Role of Surfactant Protein C in Innate Lung Defense.
Persistence of LPS-induced lung inflammation in surfactant protein-C-deficient mice.
Specimen part, Disease
View SamplesPurpose: This study was carried out to determine the consequences of the Rfx2-/- genotype on spermatogenesis in the mouse Methods: RNA was extracted from decapsulated testes of 21 day old mixed background mice of either genotype. Deep sequencing was used to determine quantitative expression of the genomes from independent replicates of each genotype Results: RNA-Seq analysis identified some 105 genes that are down regulated at least 2-fold in Rfx2-/- testes, with ~50 being reduced at least 10-fold Conclusion: Spermatogenesis undergoes complete arrest just prior to the end of the round spermatid period of sperm development in mutant mice. Sequencing results showed that approximately 105 genes were downregulated 2 fold or more in the testes of mutant mice. Comparison of similar studies of targeted mutations in genes for other transcription factor demonstrate that Rfx2 has a large and nearly unique set of genes that depend on it directly or indirectly. A large number of downregulated genes are identified with cilia function. Overall design: Testicular mRNA profiles were determined by deep sequencing using testes from 5 independent wild type and 6 independent Rfx2-/- mice
RFX2 Is a Major Transcriptional Regulator of Spermiogenesis.
No sample metadata fields
View SamplesPurpose: This study was carried out to determine the consequences of the Rfx2-/- genotype on spermatogenesis in the mouse Methods: RNA was extracted from decapsulated testes of 29-30 day old mixed background mice of either genotype. Deep sequencing was used to determine quantitative expression of the genomes from independent replicates of each genotype Results: RNA-Seq analysis identified some 640 genes that are down regulated at least 2-fold in Rfx2-/- testes, with ~150 being reduced at least 10-fold Conclusion: Spermatogenesis undergoes complete arrest just prior to the end of the round spermatid period of sperm development in mutant mice. Sequencing results showed that approximately 640 genes were downregulated 2 fold or more in the testes of mutant mice. Comparison of similar studies of targeted mutations in genes for other transcription factor demonstrate that Rfx2 has a large and nearly unique set of genes that depend on it directly or indirectly. A large number of downregulated genes are identified with cilia function. Overall design: Testicular mRNA profiles were determined by deep sequencing using testes from 5 independent wild type and 4 independent Rfx2-/- mice
RFX2 Is a Major Transcriptional Regulator of Spermiogenesis.
No sample metadata fields
View SamplesHost-environment interfaces such as the dermis comprise tissue macrophages as the most abundant resident immune cell type. Diverse tasks, i.e. to resist against invading pathogens, to attract bypassing immune cells from penetrating vessels and to aid tissue development and repair require a dynamic postnatal coordination of tissue macrophages specification. Here, we delineated the postnatal development of dermal macrophages and their differentiation into distinct subsets by adapting single cell transcriptomics, fate-mapping and tissue imaging. We thereby identified a small phenotypically and transcriptionally distinct subset of embryo-derived skin macrophages that was maintained and largely excluded from the overall postnatal exchange by monocytes. These macrophages specifically interacted with dermal sensory nerves, surveilled and trimmed the myelin sheets and regulated axon sprouting after mechanical injury. In summary, our data show long-lasting functional specification of macrophages in the dermis that is driven by step-wise adaptation to guiding structures and ensures codevelopment of ontogenetically distinct cells within the same compartment. Overall design: Single Cell Sequencing was performed on CD45+CD11b+CD64+Lin-(lineage B220, CD3, NK1.1, Siglec-F, Ly6G) CX3CR1 (low, mid, high) macrophage subsets from mouse dermis after enzymatic digestion
A Subset of Skin Macrophages Contributes to the Surveillance and Regeneration of Local Nerves.
Age, Specimen part, Cell line, Subject
View SamplesObesity and associated increased prevalence of non-alcoholic fatty liver (NAFLD) disease is suggested to be positively modulated by a high protein (HP) diet in humans and rodents. The aim was to detect mechanisms by which a HP diet prevents hepatic lipid accumulation by means of transcriptomics. To study the acute and long term effect of a high protein ingestion on hepatic lipid accumulation under both low and high fat (HF) conditions, mice were fed combinations of high (35%) or low (10%) fat and high (50%) or normal (15%) protein diets for 1 or 12 weeks. Body composition, liver fat, VLDL production rate and gene expression were investigated. Differences in metabolic processes and functions in the liver were identified using gene set enrichment analysis on microarray data. Mice fed the HP diets developed less adiposity and decreased hepatic lipid accumulation due a combination of induced processes mainly involved in protein catabolism such as transamination, TCA cycle and oxidative phosphorylation. Feeding a HP diet can successfully prevent the development of NAFLD by using ingested energy for oxidation instead of storage.
Dietary protein affects gene expression and prevents lipid accumulation in the liver in mice.
Sex, Age, Specimen part, Time
View SamplesTo further understand molecular mechanisms underlying skeletal muscle hypertrophy, expression profiles of translationally and transcriptionally regulated genes were characterized following an acute bout of maximally activated eccentric contractions. Experiments demonstrated that translational mechanisms contribute to acute gene expression changes following high resistance contractions with two candidate mRNAs, basic fibroblast growth factor (bFGF) and elongation factor-1 alpha (EF1alpha), targeted to the heavier polysomal fractions after a bout of contractions. Gene profiling was performed using Affymetrix Rat U34A GeneChips with either total RNA or polysomal RNA at one and six hours following contractions. There were 18 genes that changed expression at one hour and 70 genes that were different (60 genes increased:10 genes decreased)at six hours after contractions. The model from this profiling suggests that following high resistance contractions skeletal muscle shares a common growth profile with proliferating cells exposed to serum. This cluster of genes can be classified as "growth" genes and is commonly associated with progression of the cell cycle. However, a unique aspect was that there was induction of a cluster of tumour suppressor or antigrowth genes. We propose that this cluster of "antigrowth" genes is induced by the stress of contractile activity and may act to maintain skeletal muscle in the differentiated state. From the profiling results, further experiments determined that p53 levels increased in skeletal muscle at 6 h following contractions. This novel finding of p53 induction following exercise also demonstrates the power of expression profiling for identification of novel pathways involved in the response to muscle contraction.
Response of rat muscle to acute resistance exercise defined by transcriptional and translational profiling.
No sample metadata fields
View SamplesBackground: Moderate weight loss can ameliorate adverse health effects associated with obesity, reflected by an improved adipose tissue (AT) gene expression profile. However, the effect of rate of weight loss on the AT transcriptome is unknown.
Adipose tissue gene expression is differentially regulated with different rates of weight loss in overweight and obese humans.
Sex, Specimen part, Treatment, Subject, Time
View SamplesChildren born to diabetic and obese or overweight mothers have a higher risk of heart disease at birth and later in life. Our previous work using chromatin immunoprecipitation sequencing revealed that late-gestation diabetes in combination with maternal high fat diet causes a distinct fuel-mediated epigenetic reprogramming of cardiac tissue during fetal cardiogenesis.
Maternal High Fat Diet and Diabetes Disrupts Transcriptomic Pathways That Regulate Cardiac Metabolism and Cell Fate in Newborn Rat Hearts.
Specimen part
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