REST is a master regulator of genes that are involved in the acqusition of neuronal fate. The role of REST is not well understood so we attempted to investigate the role of REST in the development of neural cells by analysing the genes that are upregulated when REST is knocked down via shRNA
REST regulates the pool size of the different neural lineages by restricting the generation of neurons and oligodendrocytes from neural stem/progenitor cells.
Specimen part
View SamplesCD44+/CD24- subpopulation of normal and cancerous breast epithelial cells are suggested to have stem cell properties. The goal of this study was to identify gene expression differences between CD44+/CD24- and CD44-/CD24+ subpopulation of cells from a same cell lines. We selected MCF-10A cells, which are immortalized derived from a fibrocystic breast disease. These cells are immortalized but not transformed and express basal cell markers.
SLUG/SNAI2 and tumor necrosis factor generate breast cells with CD44+/CD24- phenotype.
Specimen part
View SamplesRett syndrome (RTT) is a severe neurodevelopmental disorder that is caused by mutations in the gene methyl-CpG-binding-protein-2 (MECP2). However, the molecular mechanism by which these mutations mediate the RTT neuropathology remains enigmatic. In this study, we stimulated MeCP2-null cortical neurons (in vitro) and brains (in vivo) of a RTT mouse model to explore the effect of the loss of MeCP2 function on the activity-dependent transcriptomes of the cortex and hippocampus, respectively, using RNA-seq. These analyses revealed that the loss of MeCP2 results in aberrant global pattern of gene expression, characterized predominantly by higher levels of expression of activity-dependent genes, and anomalous alternative splicing events, specifically in response to neuronal activity. Overall design: For in vitro experiments, RNA-seq was performed on MeCP2-null (MT) and wild-type (WT) neuron-enriched cortical cultures that were either treated (T) with KCl for 3hr or not treated (N), after 10 days in culture. For in vivo experiments, RNA-seq was performed on hippocampi of MeCP2-null (MT) and wild-type (WT) mice that were either treated with kainic acid for 40 or 68 minutes, or not treated.
Activity-dependent aberrations in gene expression and alternative splicing in a mouse model of Rett syndrome.
Specimen part, Treatment, Subject, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
A circadian gene expression atlas in mammals: implications for biology and medicine.
Specimen part
View SamplesTo characterize the role of the circadian clock in mouse physiology and behavior, we used RNA-seq and DNA arrays to quantify the transcriptomes of 12 mouse organs over time. We found 43% of all protein coding genes showed circadian rhythms in transcription somewhere in the body, largely in an organ-specific manner. In most organs, we noticed the expression of many oscillating genes peaked during transcriptional rush hours preceding dawn and dusk. Looking at the genomic landscape of rhythmic genes, we saw that they clustered together, were longer, and had more spliceforms than nonoscillating genes. Systems-level analysis revealed intricate rhythmic orchestration of gene pathways throughout the body. We also found oscillations in the expression of more than 1,000 known and novel noncoding RNAs (ncRNAs). Supporting their potential role in mediating clock function, ncRNAs conserved between mouse and human showed rhythmic expression in similar proportions as protein coding genes. Importantly, we also found that the majority of best-selling drugs and World Health Organization essential medicines directly target the products of rhythmic genes. Many of these drugs have short half-lives and may benefit from timed dosage. In sum, this study highlights critical, systemic, and surprising roles of the mammalian circadian clock and provides a blueprint for advancement in chronotherapy.
A circadian gene expression atlas in mammals: implications for biology and medicine.
Specimen part
View SamplesAlterations in the presence of sperm RNAs have been identified using microarrays in teratozoospermic (abnormal morphology) or other types of infertile patients. However, so far no studies had been reported on the sperm RNA content using microarrays in asthenozoospermic patients (low motility).
Differential RNAs in the sperm cells of asthenozoospermic patients.
No sample metadata fields
View SamplesThe circadian gene expression in peripheral tissue displays rhythmicity which is driven by the circadian clock and feeding-fasting cycle in mammals. In this study, circadian transcriptome was performed to investigate how fasting influences circadian gene regulation. Overall design: 8-week-old, male C57BL/6 mice were subjected to 24-hr fasting (FAST) or to ad libitum normal chow feeding (FED) under 12hr light/ 12hr dark schedule. Liver and gastrocnemius muscle were harvested every 4 hours over the circadian cycle at ZT0, 4, 8, 12, 16, 20 (n=3 per time point per group). Total RNA was extracted from liver and gastrocnemius muscle, and used for RNA-seq.
Fasting Imparts a Switch to Alternative Daily Pathways in Liver and Muscle.
Age, Cell line, Subject
View SamplesActivation of inflammatory pathways in human IBD
Activation of an IL-6:STAT3-dependent transcriptome in pediatric-onset inflammatory bowel disease.
No sample metadata fields
View SamplesWe identified miR-95 in a screen for miRNAs which functionally affect
A non-conserved miRNA regulates lysosomal function and impacts on a human lysosomal storage disorder.
Cell line
View SamplesThe nuclear receptor HNF4A regulates embryonic and post-natal hepatocyte gene expression. Using hepatocyte-specific inactivation in mice, we show that the TAF4 subunit of TFIID acts as a cofactor for HNF4A in vivo and that HNF4A interacts directly with the TAF4-TAF12 heterodimer in vitro. In vivo, TAF4 is required to maintain HNF4A-directed embryonic gene expression at post-natal stages and for HNF4A-directed activation of post-natal gene expression. TAF4 promotes HNF4A occupancy of functional cis-regulatory elements located adjacent to the transcription start sites of post-natal expressed genes and for pre-initiation complex formation required for their expression. Promoter-proximal HNF4A-TFIID interactions are therefore required for pre-initiation complex formation and stable HNF4A occupancy of regulatory elements as two concomitant mutually dependent processes. Overall design: RNA profiles in wild-type and Taf4-/- livers by deep sequencing
TAF4, a subunit of transcription factor II D, directs promoter occupancy of nuclear receptor HNF4A during post-natal hepatocyte differentiation.
No sample metadata fields
View Samples