We used microarray-based expression genomics in 25 inbred mouse strains to identify dorsal root ganglion (DRG)-expressed genetic contributors to mechanical allodynia a prominent symptom of chronic pain.
The nicotinic α6 subunit gene determines variability in chronic pain sensitivity via cross-inhibition of P2X2/3 receptors.
Sex, Age, Specimen part
View SamplesThe molecular mechanisms of Trypanosoma cruzi induced cardiac fibrosis remains to be elucidated. Primary human cardiomyoctes (PHCM) exposed to invasive T. cruzi trypomastigotes were used for transcriptome profiling and downstream bioinformatic analysis to determine fibrotic-associated genes regulated early during infection process (0 to 120 minutes). The identification of early molecular host responses to T. cruzi infection can be exploited to delineate important molecular signatures that can be used for the classification of Chagasic patients at risk of developing heart disease. Our results show distinct gene network architecture with multiple gene networks modulated by the parasite with an incline towards progression to a fibrogenic phenotype. Early during infection, T. cruzi significantly upregulated transcription factors including activator protein 1 (AP1) transcription factor network components (including FOSB, FOS and JUNB), early growth response proteins 1 and 3 (EGR1, EGR3), and cytokines/chemokines (IL5, IL6, IL13, CCL11), which have all been implicated in the onset of fibrosis. The changes in our selected genes of interest did not all start at the same time point. The transcriptome microarray data, validated by quantitative Real-Time PCR, was also confirmed by immunoblotting and customized Enzyme Linked Immunosorbent Assays (ELISA) array showing significant increases in the protein expression levels of fibrogenic EGR1, SNAI1 and IL 6. Furthermore, phosphorylated SMAD2/3 which induces a fibrogenic phenotype is also upregulated accompanied by an increased nuclear translocation of JunB. Pathway analysis of the validated genes and phospho-proteins regulated by the parasite provides the very early fibrotic interactome operating when T. cruzi comes in contact with PHCM. The interactome architecture shows that the parasite induces both TGF- dependent and independent fibrotic pathways, providing an early molecular foundation for Chagasic cardiomyopathy. Examining the very early molecular events of T. cruzi cellular infection may provide disease biomarkers which will aid clinicians in patient assessment and identification of patient subpopulation at risk of developing Chagasic cardiomyopathy.
Early Regulation of Profibrotic Genes in Primary Human Cardiac Myocytes by Trypanosoma cruzi.
Specimen part
View SamplesSpecial AT-rich binding protein 1 (SATB1) is a global chromatin organizer and a transcription factor induced by interleukin-4 (IL-4) during the early T helper 2 (Th2) cell differentiation. In this study, we investigated the role of SATB1 in T helper cell differentiation by performing gene expression profiling of human differentiating Th cells in which expression of SATB1 was downregulated by RNA interference (RNAi). Our results indicate that SATB1 is involved in the regulation of more than three hundred genes in primary human CD4+ T cells, including several IL-12 and/or IL-4 regulated factors, suggesting a role in the development or function of Th subtypes.
SATB1 dictates expression of multiple genes including IL-5 involved in human T helper cell differentiation.
No sample metadata fields
View SamplesLeptospirosis is a neglected zoonotic disease of global importance. Despite its prevalence, pathogenesis is still poorly understood. Our aim was to discover transcripts responsable for pathogenicity of leptospirosis. We compared the transcriptome profiles of saprophyte, attenuated and virulent strain of Leptospira spp.
Transcriptome datasets of macrophages infected with different strains of <i>Leptospira</i> spp.
Cell line
View SamplesComparison of transcriptional profiles of human umbilical vein endothelial cells (HUVECs) expressing wild-type vs. VM-causative mutant forms of TIE2/TEK.
Venous malformation-causative TIE2 mutations mediate an AKT-dependent decrease in PDGFB.
Specimen part
View SamplesTranscriptome analysis of gastrocnemius muscle RNA samples from exercise and sedentary ancestries
Sex-specific effects of exercise ancestry on metabolic, morphological and gene expression phenotypes in multiple generations of mouse offspring.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid progenitors.
Specimen part
View SamplesHere we show that hematopoietic transcription factors Scl, Lmo2, Runx1 and Bmi1 can convert a developmentally-distant lineage (fibroblasts) into induced hematopoietic progenitors (iHPs). We analyzed transcriptomic data for cell undergoing the transdifferentiation process at several time-points of the process.
Reprogramming mouse fibroblasts into engraftable myeloerythroid and lymphoid progenitors.
Specimen part
View SamplesThe EMT program allows epithelial cells to become endowed with motility, invasiveness and stem cell traits. We investigated difference in signaling networks that are differentially utilized in EMTed and non-EMTed cells, thereby identifying therapeutic targets that are unique to EMT/cancer stem cells.
Protein kinase C α is a central signaling node and therapeutic target for breast cancer stem cells.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Whole-Genome and Epigenomic Landscapes of Etiologically Distinct Subtypes of Cholangiocarcinoma.
Specimen part
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