In the current study, we performed transcriptome profiling of the mouse PFC to determine the dynamic changes in the Prefrontal cortex (PFC)after repeated cocaine treatment. In the current study, we observed dynamic changes in the transcriptome profiling of the PFC of repeated-cocaine treated mice, and found that distinct pathways were involved in the acute, sub-acute, and chronic stages of cocaine withdrawal. The main findings of our results include: 1) energy metabolism and protein metabolism pathways showed gradual or fluctuant decrease after cocaine withdrawal; 2) ERK pathway showed persistent changes after cocaine withdrawal; 3) plasticity related pathways, such as long-term potentiation, the regulation of the actin cytoskeleton, and the axon guidance pathway, showed a fluctuant increase after cocaine withdrawal. Our results suggest that maladaptive neural plasticity associated with psychostimulant dependence may be an ongoing degenerative process with dynamic changes in the gene network at different stages of withdrawal. Overall design: The bilateral PFC was excised from each animal at either 2 h, 24 h, or 7 days after the final injection of cocaine. To account for inter-animal variations, we obtained 2 biological replicates for each treatment group, with each replicate representing the PFCs pooled from 5 animals. Pair-end 75-nt sequencing was performed using the Illumina HiSeq2000.
Dynamic Expression Changes in the Transcriptome of the Prefrontal Cortex after Repeated Exposure to Cocaine in Mice.
Age, Specimen part, Cell line, Treatment, Subject
View SamplesHow animals coordinate gene expression in response to starvation is an outstanding problem closely linked to aging, obesity, and cancer. Newly hatched Caenorhabditis elegans respond to food deprivation by halting development and promoting long-term survival (L1 diapause), thereby providing an excellent model to study starvation response. Through a genetic search, we have discovered that the tumor suppressor Rb critically promotes survival during L1 diapause and likely does so by regulating the expression of genes in both insulin-IGF-1 signaling (IIS)-dependent and -independent pathways mainly in neurons and the intestine. Global gene expression analyses suggested that Rb maintains the starvation-induced transcriptome and represses the re-feeding induced transcriptome, including the repression of many pathogen/toxin/oxidative stress-inducible and metabolic genes, as well as the activation of many other stress-resistant genes, mitochondrial respiratory chain genes, and potential IIS receptor antagonists. Notably, the majority of genes dysregulated in starved L1 Rb(-) animals were not found to be dysregulated in fed conditions. Together, these findings identify Rb as a critical regulator of the starvation response and suggest a link between functions of tumor suppressors and starvation survival. These results may provide mechanistic insights into why cancer cells are often hypersensitive to starvation treatment.
The tumor suppressor Rb critically regulates starvation-induced stress response in C. elegans.
No sample metadata fields
View SamplesThis study aimed to identify differential expressed genes before and after treatment with the compound sulforaphene, using the MDA-MB-453 breast cancer cell line as a model.
Sulforaphene inhibits triple negative breast cancer through activating tumor suppressor Egr1.
Sex, Age, Specimen part, Cell line, Race
View SamplesAs part of a genomic profiling study of CRCs with MSI, we have performed genome-wide expression analyses of a consecutive patient series.
Multilevel genomics of colorectal cancers with microsatellite instability-clinical impact of JAK1 mutations and consensus molecular subtype 1.
Specimen part
View SamplesFrom our previous data, we found that loss of ATAD3A gene expression in breast cancer cells results in loss of cell motility in vitro and metastasis in vivo. To obtain a better understanding of oncogenic pathway of ATAD3A, we have established the stable ATAD3A knockdown MDA-MB-231 cells using lentiviral strategy.
Mitochondrial ATAD3A combines with GRP78 to regulate the WASF3 metastasis-promoting protein.
Cell line
View SamplesLymphatic malformation (LM) is a developmental anomaly of the lymphatic system that may lead to disfigurement, organ dysfunction and recurrent infection. Though several treatment modalities exist, pharmacotherapy is often associated with side effects and recurrence is common following surgical interventions. Moreover, despite the recent discovery of PIK3CA mutations in lymphatic endothelial cells of LM patients, the full spectrum of molecular pathways involved in LM pathogenesis is poorly understood. Here, we performed RNA sequencing on blood samples obtained from ten LM patients and nine healthy subjects and found 421 differentially expressed genes that stratify LM subjects from healthy controls. Using this LM gene signature, we identified novel pathway alterations in LM, such as oxidative phosphorylation, MEK/ERK, bone morphogenetic protein (BMP), and Wnt/b-catenin pathways, in addition to confirming the known alterations in cell cycle and the PI3K/AKT pathway. Furthermore, we performed computational drug repositioning analysis to predict existing therapies (e.g. sirolimus) and novel classes of drugs for LM. These findings deepen our understanding of LM pathogenesis and may facilitate non-invasive diagnosis, pathway analysis and therapeutic development. Overall design: RNA-sequencing of peripheral blooof 10 LM patients and 9 control subjects
Alterations of the MEK/ERK, BMP, and Wnt/β-catenin pathways detected in the blood of individuals with lymphatic malformations.
Disease, Disease stage, Subject
View SamplesStreptococcus suis serotype 2 (SS2), a major swine pathogen and an emerging zoonotic agent, has greatly challenged global public health. Systematical information about host immune response to the infection is important for understanding the molecular mechanism of diseases.
Response of swine spleen to Streptococcus suis infection revealed by transcription analysis.
Specimen part
View SamplesOur understanding of cellular mechanisms by which animals regulate their response to starvation is limited despite the close relevance of the problem to major human health issues. L1 diapause of Caenorhabditis elegans, where newly hatched first stage larval arrested in response to food-less environment, is an excellent system to study the problem. We found through genetic manipulation and lipid analysis that ceramide biosynthesis, particularly those with longer fatty acid side chains, critically impacts animal survival during L1 diapause. Genetic and expression analyses indicate that ceramide likely regulate this response by affecting gene expression and activity in multiple regulatory pathways known to regulate starvation-induced stress, including the insulin-IGF-1 signaling (IIS) pathway, Rb and other pathways that mediate pathogen/toxin/oxidative stress responses. These findings provide an important insight into the roles of sphingolipid metabolism in not only starvation response but also aging and food-response related human health problems.
Starvation-Induced Stress Response Is Critically Impacted by Ceramide Levels in Caenorhabditis elegans.
No sample metadata fields
View SamplesUnraveling complexity of DNA methylome is essential to decipher DNA methylation mechanism in life. However, this has been subjected to technological constraints to balance between cost and accurate measurement of the DNA methylation level. In this study, by innovatively introducing C-hydroxylmethylated adapters, we have developed MeDIP-Bisulfite sequencing (MB-seq), which could obtain DNA methylome of repertoire CpGs at single-base resolution. We found MB-seq only costs 10% of MethylC-seq, but covers 85% of total CpGs in human genome. Unlike absolute methylation levels determined by MethylC-seq and RRBS, MB-seq presented relative methylation levels that are linearly inflated. This has enlightened us to develop a MB-seq corresponding correction method for methylation level based on ridge regression, which integrates the data of MB-seq and RRBS to predict the methylation level of total 28.2 million CpGs on human genome with high accuracy (Pearson correlation coefficient, PCC=0.90). Moreover, by employing MB-seq, we generated the DNA methylome of an ovarian epithelial cell line (T29) and its oncogenic counterpart (T29H), respectively. After ridge regression, we identified 131,790 differential methylation regions (DMRs) with high accuracy between T29 and T29H, far more than 7,567 obtained from RRBS. Taken together, our result demonstrated that the MB-seq combined with ridge regression is a wide applicable approach for profiling of DNA methylome. Overall design: Total RNAs were extracted from T29 and T29H with RNeasy Mini Kit (QIAGEN, Germany). RNA quality was quality-controlled by Bioanalyser 2100 (RNA nano kits, Agilent). mRNA-Seq libraries were generated from total RNA with polyA+ selection of mRNA using the TruSeq RNA Sample Prep Kit v2 (Illumina, San Diego, CA), and then subjected to transcriptome sequencing on the Illumina Hiseq 2000
MBRidge: an accurate and cost-effective method for profiling DNA methylome at single-base resolution.
No sample metadata fields
View SamplesBone development and regeneration is associated with the Wnt signaling pathway that, according to literature, can be modulated by lithium ions (Li+). The aim of this study was to evaluate the gene expression profile during peri-implant healing of poly(lactic-co-glycolic acid) (PLGA) implants with incorporated Li+, while PLGA without Li+ was used as control, and a special attention was then paid to the Wnt signaling pathway. The implants were inserted in rat tibia for 7 or 28 days and the gene expression profile was investigated using a genome-wide microarray analysis. The results were verified by qPCR and immunohistochemistry. Histomorphometry was used to evaluate the possible effect of Li+ on bone regeneration. The microarray analysis revealed a large number of significantly differentially regulated genes over time within the two implant groups. The Wnt signaling pathway was significantly affected by Li+, with approximately 34% of all Wnt-related markers regulated over time, compared to 22% for non-Li+ containing (control; Ctrl) implants. Functional cluster analysis indicated skeletal system morphogenesis, cartilage development and condensation as related to Li+. The downstream Wnt target gene, FOSL1, and the extracellular protein-encoding gene, ASPN, were significantly upregulated by Li+ compared with Ctrl. The presence of -catenin, FOSL1 and ASPN positive cells was confirmed around implants of both groups. Interestingly, a significantly reduced bone area was observed over time around both implant groups. The presence of periostin and calcitonin receptor-positive cells was observed at both time points. This study is to the best of the authors knowledge the first report evaluating the effect of a local release of Li+ from PLGA at the fracture site. The present study shows that during the current time frame and with the present dose of Li+ in PLGA implants, Li+ is not an enhancer of early bone growth, although it affects the Wnt signaling pathway.
Gene expression profiling of peri-implant healing of PLGA-Li+ implants suggests an activated Wnt signaling pathway in vivo.
Sex, Specimen part, Treatment, Time
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