The E2A transcription factors promote the development of thymus-seeding cells but it remains unknown whether these proteins play a role in T lymphocyte lineage specification or commitment. By examining E2A-dependent genes in developing T cells, we will address whether these proteins are involved in these processes.
E2A transcription factors limit expression of Gata3 to facilitate T lymphocyte lineage commitment.
Specimen part
View SamplesTime-course analysis of adipocyte gene expression profiles response to high fat diet. The hypothesis tested in the present study was that in diet-induced obesity, early activation of TLR-mediated inflammatory signaling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches targeting visceral adipose tissue genes altered early by HFD feeding may help ameliorate the deleterious effects of a diet-induced obesity.
Time-course microarrays reveal early activation of the immune transcriptome and adipokine dysregulation leads to fibrosis in visceral adipose depots during diet-induced obesity.
Age, Specimen part, Treatment, Time
View SamplesCore diet-induced obesity networks were constructed using Ingenuity pathway analysis (IPA) based on 332 high-fat diet responsive genes identified in liver by time-course microarray analysis (8 time-points over 24 weeks) of high-fat diet fed mice compared to normal diet fed mice. IPA identified five core diet-induced obesity networks with time-dependent gene expression changes in liver. When we merged core diet-induced obesity networks, Tlr2, Cd14 and Ccnd1 emerged as hub genes associated with both liver steatosis and inflammation and were altered in a time-dependent manner. Further protein-protein interaction network analysis revealed Tlr2, Cd14 and Ccnd1 were inter-related through the ErbB/insulin signaling pathway. Dynamic changes occur in molecular networks underlying diet-induced obesity. Tlr2, Cd14 and Ccnd1 appear to be hub genes integrating molecular interactions associated with the development of NASH. Therapeutics targeting hub genes and core diet-induced obesity networks may help ameliorate diet-induced obesity and NASH.
Time-dependent network analysis reveals molecular targets underlying the development of diet-induced obesity and non-alcoholic steatohepatitis.
Age, Specimen part
View SamplesHigh grade serous carcinoma (HGSC) arising from either the fallopian tube or ovary has a poor prognosis primarily due to its early dissemination throughout the abdominal cavity. Genomic and proteomic approaches have provided snapshots of the proteogenomics of ovarian cancer (OvCa)1,2, but a systematic examination of both the tumor and stromal compartments is critical to understanding OvCa metastasis. We developed a label-free proteomic workflow to analyze as few as 5,000 formalin-fixed, paraffin embedded cells microdissected from each compartment. The tumor proteome was comparatively stable during progression from in situ lesions to metastatic disease; however, the metastasis-associated stroma was characterized by a highly conserved proteomic signature, prominently including the methyltransferase nicotinamide N-methyltransferase (NNMT) and the proteins it regulates. Stromal NNMT expression was necessary and sufficient for several functional aspects of the cancer associated fibroblast (CAF) phenotype, including the expression of CAF markers and the secretion of cytokines and oncogenic extracellular matrix. Stromal NNMT supported OvCa migration, proliferation, and in vivo growth and metastasis. Expression of NNMT in CAFs led to a depletion of S-adenosyl methionine (SAM) and a reduction in histone methylation associated with extensive gene expression changes in the tumor stroma. This work supports the use of ultra-low input proteomics to identify candidate drivers of disease phenotypes and reveals that NNMT is a central, metabolic regulator of CAF differentiation and cancer progression in the stroma and a novel treatment target. Overall design: Three biological replicates of normal murine 3T3 fibroblasts expressing either control or NNMT overexpression construct were grown for 48 hours in physiological levels of methionine before RNA was collected and sequenced to identify genes differentially regulated in response to NNMT.
Proteomics reveals NNMT as a master metabolic regulator of cancer-associated fibroblasts.
Cell line, Subject
View SamplesPharmacological and gene ablation studies have demonstrated a crucial role of the cardiac natriuretic peptides (NP) hormones ANF and BNP in the maintenance of cardiovascular homeostasis. In addition, hypertension and chronic congestive heart failure are clinical entities that may be regarded as states of relative NP deficiency. Hence the study of the function of the endocrine heart is highly relevant.
Transcriptional analysis of the mammalian heart with special reference to its endocrine function.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Ras dexamethasone-induced protein 1 is a modulator of hormone secretion in the volume overloaded heart.
No sample metadata fields
View SamplesPharmacological and gene ablation studies have demonstrated a crucial role of the caridac natriuretic peptides (NP) hormones ANF and BNP in the maintenance of cardiovascular homeostasis. Considerable effort has been focused on the elucidation of the mechanistic underlying increased atrial ANF and BNP expression and secretion. These investigations are important because under chronic congestive heart failure, the secretion of NPs although increased and beneficial, is relatively insufficient as demonstrated by the fact that patients benefit form the unloading of the heart induced by therapeutic administration of either ANF or BNP.
Ras dexamethasone-induced protein 1 is a modulator of hormone secretion in the volume overloaded heart.
No sample metadata fields
View SamplesPharmacological and gene ablation studies have demonstrated a crucial role of the caridac natriuretic peptides (NP) hormones ANF and BNP in the maintenance of cardiovascular homeostasis. Considerable effort has been focused on the elucidation of the mechanistic underlying increased atrial ANF and BNP expression and secretion. These investigations are important because under chronic congestive heart failure, the secretion of NPs although increased and beneficial, is relatively insufficient as demonstrated by the fact that patients benefit form the unloading of the heart induced by therapeutic administration of either ANF or BNP.
Ras dexamethasone-induced protein 1 is a modulator of hormone secretion in the volume overloaded heart.
No sample metadata fields
View SamplesEmbryonic retinal development Overall design: Mouse retinas at different embryonic developmental stages were isolated and mRNA expression was determined by RNA sequencing
Programmed mitophagy is essential for the glycolytic switch during cell differentiation.
Specimen part, Cell line, Subject
View SamplesThe transcription factor Snail has been proposed to mediate epithelial-to-mesenchymal transition (EMT) and confer mesenchymal invasive phenotype to epithelial cancer cells
SNAIL-induced epithelial-to-mesenchymal transition produces concerted biophysical changes from altered cytoskeletal gene expression.
Specimen part, Cell line
View Samples