Embryonic 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 SamplesGenome-wide approach to identify the cell-autonomous role of Snf2h in lens fiber cell terminal differentiation. Differential gene expression was analyzed in Snf2h lens-conditional knockout and wildtype newborn mouse eyeballs, with subsequent comparison of this data with the Brg1 lens-conditional knockout mouse eyes expression data (GSE25168).
Chromatin remodeling enzyme Snf2h regulates embryonic lens differentiation and denucleation.
No sample metadata fields
View SamplesDysfunctional mitochondria and generation of reactive oxygen species (ROS) promote chronic diseases, which have spurred interest in the molecular mechanisms underlying these conditions. Previously, we have demonstrated that disruption of post-translational modification of proteins with ß-linked N-acetylglucosamine (O- glcnAcylation) via overexpression of the O-glcnAc–regulating enzymes O- glcnAc transferase (OGT) or O- glcnAcase (OGA) impairs mitochondrial function. Here, we report that sustained alterations in O- glcnAcylation either by pharmacological or genetic manipulation also alters metabolic function. Sustained O-glcnAc elevation in SH-SY5Y neuroblastoma cells increased OGA expression and reduced cellular respiration and ROS generation. Cells with elevated O-glcnAc levels had elongated mitochondria and increased mitochondrial membrane potential, and RNA-Seq in SH-SY5Y cells indicated transcriptome reprogramming and down regulation of the NRF2-mediated antioxidant response. Sustained O-glcnAcylation in mice brain and liver validated the metabolic phenotypes observed in the cells, and OGT knockdown in the liver elevated ROS levels, impaired respiration, and increased the NRF2 antioxidant response. Moreover, elevated O-glcnAc levels promoted weight loss and lowered respiration in mice and skewed the mice toward carbohydrate-dependent metabolism as determined by indirect calorimetry. In summary, sustained elevation in O-glcnAcylation coupled with increased OGA expression reprograms energy metabolism, a finding that has potential implications for the etiology, development, and management of metabolic diseases. Overall design: SY5Y cells were adapted to long term O-glcnAcase (OGA) inhibition using the specific OGA inhibitor Thiamet-G (tmg) or glucosamine treatment for 3 weeks. After adaptation to the growth conditions, cells were harvest and RNA isolated for Next Generation RNA sequencing. Briefly, cDNA library was prepared using Illumina TruSeq Stranded mRNA sample preparation kit (Illumina) as manufacturer's instruction. Total RNA was isolated using the same method as previously described and 800 ng of the total RNA per reaction was used to initiate the protocol. The quality of RNA sequencing results was first assessed using FastQC (0.11.2). RSEM (1.2.22) was utilized to align the reads to the human reference genome HG38 and to calculate gene expression values. EdgeR (3.14.0) was then used to normalize the expression values using the TMM-method (weighted trimmed mean of M-values), and for differential expression analyses. First, the negative binomial conditional common likelihood was maximized to estimate a common dispersion value across all genes (estimateCommonDisp). Next, tagwise dispersion values were estimated by an empirical Bayes method based on weighted conditional maximum likelihood (estimateTagwiseDisp). Finally, the differentially gene expression was calculated by computing genewise exact tests for differences in the means between two groups of negative-binomially distributed counts. Hierarchical clustering analysis was determined using Euclidean distance. The following R-packages were utilized for calculations and visualizations: plots and edgeR.
Sustained <i>O-</i>GlcNAcylation reprograms mitochondrial function to regulate energy metabolism.
Specimen part, Cell line, Subject
View SamplesThe 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 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 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 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 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 Samples