Transcriptomic response of mouse mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin D3
The transcriptomic response of mixed neuron-glial cell cultures to 1,25-dihydroxyvitamin d3 includes genes limiting the progression of neurodegenerative diseases.
Specimen part, Treatment
View SamplesAnalysis of estrogen receptor (ER)-positive MCF7 cell total RNA expression and polysome-assiciated RNA expression following treatment with estradiol (E2) and vehicle (etoh).
Estrogen coordinates translation and transcription, revealing a role for NRSF in human breast cancer cells.
Cell line
View SamplesA Single Cell Analysis of Myogenic Dedifferentiation Induced by Small Molecules An important direction in chemical biology is the derivation of compounds that affect cellular differentiation or its reversal. The fragmentation of multinucleate myofibers into viable mononucleates (called cellularisation) occurs during limb regeneration in urodele amphibians and the isolation of myoseverin, a tri-substituted purine that could apparently activate this pathway of myogenic dedifferentiation in mammalian cells, generated considerable interest. We have explored the mechanism and outcome of cellularisation at a single cell level, and report findings that significantly extend the previous work with myoseverin. Using a panel of compounds, including a novel triazine compound called 109 with structural similarity and comparable activity to myoseverin, we have identified microtubule disruption as critical for activation of the response. Our analysis has included the related control triazine compound 401, and the microtubule disrupting agent nocodazole. Time-lapse microscopy has enabled us to analyse the fate of identified mononucleate progeny, and directly assess the extent of dedifferentiation.
A single-cell analysis of myogenic dedifferentiation induced by small molecules.
Specimen part, Cell line, Compound, Time
View SamplesAnalysis of tissues of DBA/2 mice fed a standard breeding diet (SBD) and high fat diet (HFD) revealed tissue specific roles in inflammation and disease, and altered communication between tissues. The tissues surveyed incuded adipose tissues (brown, inguinal, mesenteric, retro-peritoneal, subcutaneious and gonadal), muscle and liver.
High-fat diet leads to tissue-specific changes reflecting risk factors for diseases in DBA/2J mice.
Specimen part, Treatment
View SamplesSilencing HoxA1 in vivo by intraductal delivery of nanoparticle-formulated siRNA reduced mammary tumor incidence by 75% , reduced cell proliferation, and prevented loss of ER and PR expression.
Silencing HoxA1 by intraductal injection of siRNA lipidoid nanoparticles prevents mammary tumor progression in mice.
Age, Specimen part
View SamplesPurpose: In all vertebrates, the thymus is necessary and sufficient for production of classic adaptive T cells. The key components of the thymus are cortical and medullary thymic epithelial cells (cTECs and mTECs). Despite the capital role of TECs, our understanding of TEC biology is quite rudimentary. For instance, we ignore what might be the extent of divergence in the functional program of these two TECs populations. It also remains unclear why the number of TECs decreases rapidly with age, thereby leading to progressive thymic insufficiency. Methods: Systems level understanding of cell function begins with gene expression profiling, and the transcriptome is currently the only ''-ome'' that can be reliably tackled in its entirety in freshly harvested primary cells. In order to gain novel insights into TEC biology, we therefore decided to analyse the whole transcriptome of cTECs, mTECs and skin epithelial cells. We elected to analyse gene expression using RNA-seq rather microarrays because RNA-seq has higher sensitivity and dynamic range coupled to lower technical variations. Results: Our deep sequencing approach provides a unique perspective into the transcriptome of TECs. Consistent with their ability to express ectopic genes, we found that mTECs expressed more genes than other cell populations. Out of a total of 15,069 genes expressed in TECs, 25% were differentially expressed by at least 5-fold in cTECs vs. mTECs. Genes expressed at higher levels in cTECs than mTECs regulate numerous cell functions including cell differentiation, cell movement and microtubule dynamics. Almost all positive regulators of the cell cycle were overexpressed in skin ECs relative to TECs. Conclusions: Our RNA-seq data provide novel insights into the transcriptional landscape of TECs, highlight substantial divergences in the transcriptome of TEC subsets and suggest that cell cycle progression is differentially regulated in TECS and skinECs. We believe that our work will therefore represent a valuable resource and will be of great interest to readers working in biological sciences, particularly in the areas of immunology and systems biology. Overall design: The mRNA profiles of cTEC, mTEC (from 14 thymi of 7-days old C57BL/6 mice) and skinEC (from the trunk and dorsum of seven newborn mice) were generated by RNA-sequencing using Illumina HiSeq2000.
Transcriptome sequencing of neonatal thymic epithelial cells.
Specimen part, Cell line, Subject
View SamplesPurpose: The ability to rationally manipulate the transcriptional states of cells would be of great use in medicine and bioengineering. We have developed a novel algorithm, NetSurgeon, which utilizes genome-wide gene regulatory networks to identify interventions that force a cell toward a desired expression state. Results: We used NetSurgeon to select transcription factor deletions aimed at improving ethanol production in S. cerevisiae cultures that are catabolizing xylose. We reasoned that interventions that move the transcriptional states of cells utilizing xylose toward the fermentative state typical of cells that are producing ethanol rapidly (while utilizing glucose) might improve xylose fermentation. Some of the interventions selected by NetSurgeon successfully promoted a fermentative transcriptional state in the absence of glucose, resulting in strains with a 2.7-fold increase in xylose import rates, a 4-fold improvement in xylose integration into central carbon metabolism, or a 1.3-fold increase in ethanol production rate. Conclusions: We conclude by presenting an integrated model of transcriptional regulation and metabolic flux that will enable future metabolic engineering efforts aimed at improving xylose fermentation to prioritize functional regulators of central carbon metabolism. Overall design: Mutant and wildtype S. cerevisiae cells were put into 48 hour aerobic batch fermentations of synthetic complete medium supplmented with 2% glucose and 5% xylose and culture samples were taken at 4 hours and 24 hours for transcriptional profiling performed by RNA-Seq analysis. In addition, wildtype S. cerevisiae cells were grown in various single carbon sources for 12 hours and culture samples were taken for transcriptional profiling performed by RNA-Seq analysis.
Model-based transcriptome engineering promotes a fermentative transcriptional state in yeast.
Subject
View SamplesThe homeobox containing gene Arx is expressed during ventral telencephalon development and it is required for correct GABAergic interneuron tangential migration from the ganglionic eminences to the olfactory bulbs, cerebral cortex and striatum. Its human ortholog is associated with a variety of neurological clinical manifestations whose syntoms are compatible with a loss of cortical interneurons and altered basal ganglia related-activities in humans. Herein, we reported the identification by global expression profiling of a group of genes whose expression is consistently altered in Arx mutant ganglionic eminences. Following analysis revealed the striking ectopic expression in the ganglionic eminences of a number of genes normally not, or only marginally, expressed in the ventral telencephalon. Among them, we functionally analyzed Ebf3, whose ectopic expression in ventral telencephalon is preventingneuronal tangential migration. Further, we showed that Arx is sufficient to repress Ebf3 endogenous expression and that its silencing in Arx mutant tissue might marginally rescue tangential cell movements. Together, these data provide an initial analysis of the molecular pathways regulated by Arx and how their networking might regulate those specific cellular processes during telencephalon development strongly altered by loss of Arx.
Arx acts as a regional key selector gene in the ventral telencephalon mainly through its transcriptional repression activity.
No sample metadata fields
View SamplesAQM shows acute muscle wasting and weakness. Key aspects of AQM include muscle atrophy and myofilament loss. Gene expression profiling, using muscle biopsies from AQM, neurogenic atrophy and normal controls, showed that both myogenic and neurogenic atrophy share induction of myofiber-specific ubiquitin/proteosome pathways while only the AQM shows a specific strong induction of transforming growth factor (TGF)-beta/MAPK pathways.
Constitutive activation of MAPK cascade in acute quadriplegic myopathy.
No sample metadata fields
View SamplesFew studies have investigated heterogeneity of selection response in replicate lines subjected to equivalent selection. We developed 4 replicate lines of mice based on high levels of voluntary wheel running (high runner or HR lines) while also maintaining 4 non-selected control lines. This led to the unexpected discovery of the HR mini-muscle (HRmini) phenotype, recognized by a 50% reduction in hindlimb muscle mass, which became fixed in 1 of the 4 HR selected lines.
Gene expression profiling of gastrocnemius of "minimuscle" mice.
Sex, Specimen part
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