The innate immune system is the organisms first line of defense against pathogens. Pattern recognition receptors (PRRs) are responsible for sensing the presence of pathogen-associated molecules. The prototypic PRRs, the membrane-bound receptors of the Toll-like receptor (TLR) family, recognize pathogen-associated molecular patterns (PAMPs) and initiate an innate immune response through signaling pathways that depend on the adaptor molecules MyD88 and TRIF. Deciphering the differences in the complex signaling events that lead to pathogen recognition and initiation of the correct response remains challenging. Here we report the discovery of temporal changes in the protein signaling components involved in innate immunity. Using an integrated strategy combining unbiased proteomics, transcriptomics and macrophage stimulations with three different PAMPs, we identified differences in signaling between individual TLRs and revealed specifics of pathway regulation at the protein level. In addition to forming macrophages and dendritic cells, monocytes in adult peripheral blood retain the ability to develop into osteoclasts, mature bone-resorbing cells. The extensive morphological and functional transformations that occur during osteoclast differentiation require substantial reprogramming of gene and protein expression. Here we employ -omic-scale technologies to examine in detail the molecular changes at discrete developmental stages in this process (precursor cells, intermediate osteoclasts, and multinuclear osteoclasts), quantitatively comparing their transcriptomes and proteomes.
Characterization of functional reprogramming during osteoclast development using quantitative proteomics and mRNA profiling.
Specimen part, Cell line
View SamplesResults from clinical and imaging studies provide evidence for changes in schizophrenia with disease progression, however, the underlying molecular differences that may occur at different stages of illness have not been investigated. To test the hypothesis that the molecular basis for schizophrenia changes from early to chronic illness, we profiled genome-wide expression patterns in prefrontal cortex of schizophrenic subjects at different stages of illness, along with their age- and sex-matched controls. Results show that gene expression profiles change dramatically depending on the stage of illness, whereby the greatest number and magnitude of gene expression differences were detected in subjects with short-term illness ( 4 years from diagnosis). Comprehensive pathways analyses revealed that each defined stage of illness was associated with dysfunction in both distinct, as well as overlapping systems. Short-term illness was particularly associated with disruptions in gene transcription, metal ion binding, RNA processing and vesicle-mediated transport. In contrast, long-term illness was associated with inflammation, stimulus-response and immune functions. We validated expression differences of 12 transcripts associated with these various functions by real-time PCR analysis. While only four genes, SAMSN1, CDC42BPB, DSC2 and PTPRE, were consistently expressed across all groups, there was dysfunction in overlapping systems among all stages, including cellular signal transduction, lipid metabolism and protein localization. Our results demonstrate that the molecular basis for schizophrenia changes from early to chronic stages, providing evidence for a changing nature of schizophrenia with disease progression.
Molecular profiles of schizophrenia in the CNS at different stages of illness.
Sex, Age
View SamplesThis study was designed to define erythropoietin (EPO) regulated genes in murine bone marrow erythroid progenitor cells at two stages of development, designated E1, and E2. E1 cells correspond to CFUe- like progenitors, while E2 cells are proerythroblasts.
Defining an EPOR- regulated transcriptome for primary progenitors, including Tnfr-sf13c as a novel mediator of EPO- dependent erythroblast formation.
Sex, Specimen part, Treatment
View SamplesSingle-neuron transcriptome profiles of Dorsal Raphe neurons marked by a history of expression of Drd2::Cre and Pet1::Flpe (GFP+), as well as Dorsal Raphe neurons marked by a history of Pet1::Flpe expression only (mCherry+). Overall design: GFP and mCherry expressing neurons from triple transgenic Drd2::Cre;Pet1::Flpe;RC:FrePe mice were acutely dissociated, manually sorted, and single-neuron RNA-seq was performed (17 GFP+ cells, 8 mCherry+ cells).
Identification of Serotonergic Neuronal Modules that Affect Aggressive Behavior.
Specimen part, Subject
View SamplesWe used microarrays to compare gene expression between three HRAS-wild type lines (13, 162d, 165d) and three HRAS-G12S mutant lines (7, 8, 16).
Dysregulation of astrocyte extracellular signaling in Costello syndrome.
Specimen part
View Samplesab and gd T cells originate from a common, multi-potential precursor population in the thymus, but the molecular mechanisms regulating this lineage fate decision process are unknown. We have identified Sox13 as a gd-specific gene in the immune system. Using Sox13 transgenic mice, we show that SOX13 promotes gd T cell development while opposing ab T cell differentiation. Conversely, mice deficient in Sox13 expression exhibited impaired development of gd T cells, but not ab T cells. One mechanism of SOX13 function is the inhibition of WNT/TCF signaling, suggesting that differential WNT/TCF activity is an essential parameter for this binary cell fate choice.
Regulation of gammadelta versus alphabeta T lymphocyte differentiation by the transcription factor SOX13.
Sex, Age, Specimen part
View SamplesTranscriptome analysis of BORIS depleted MCF7 cells
Intragenic DNA methylation and BORIS-mediated cancer-specific splicing contribute to the Warburg effect.
No sample metadata fields
View SamplesIdentification of differentially expressed genes upon treatment with Eltrombopag in HL60 cells. HL60 cells were untreated, or treated with 3ug/ml of Eltrombopag for 36 hrs in RPMI with 10% FBS
Eltrombopag inhibits the proliferation of leukemia cells via reduction of intracellular iron and induction of differentiation.
Specimen part, Cell line
View SamplesThis study is aimed in identification of gene expression profiles in cervical cancer and the role of specific genes in cervical carcinogenesis.
Identification of copy number gain and overexpressed genes on chromosome arm 20q by an integrative genomic approach in cervical cancer: potential role in progression.
No sample metadata fields
View SamplesNeurospheres generated in vitro were treated with non-epinephrine or potassium chloride. Gene expression analysis was then carried out to identify genes that are up or down regulated due to chemical treatement.
A comparative study of techniques for differential expression analysis on RNA-Seq data.
Sex, Specimen part
View Samples