Pseudomonas fluorescens strain SS101 (Pf.SS101) promotes growth of Arabidopsis thaliana, enhances greening and lateral root formation, and induces systemic resistance (ISR) against the bacterial pathogen Pseudomonas syringae pv. tomato (Pst). Here, targeted and untargeted approaches were adopted to identify bacterial determinants and underlying mechanisms involved in plant growth promotion and ISR by Pf.SS101. Based on targeted analyses, no evidence was found for volatiles, lipopeptides and siderophores in plant growth promotion by Pf.SS101. Untargeted, genome-wide analyses of 7,488 random transposon mutants of Pf.SS101 led to the identification of 21 mutants defective in both plant growth promotion and ISR. Many of these mutants, however, were auxotrophic and impaired in root colonization. Genetic analysis of three mutants followed by site-directed mutagenesis, genetic complementation and plant bioassays revealed the involvement of the phosphogluconate dehydratase gene edd, the response regulator gene colR and the adenylsulfate reductase gene cysH in both plant growth promotion and ISR. Subsequent comparative plant transcriptomics analyses strongly suggest that modulation of sulfur assimilation, auxin biosynthesis and transport, steroid biosynthesis and carbohydrate metabolism in Arabidopsis are key mechanisms linked to growth promotion and ISR by Pf.SS101.
Genome-wide analysis of bacterial determinants of plant growth promotion and induced systemic resistance by Pseudomonas fluorescens.
Specimen part, Treatment
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The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.
Sex, Age, Specimen part, Disease
View SamplesIn the present study we analyzed the effect of primary osteoporosis and advanced donor age on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from bone marrow. Human MSC of elderly patients suffering from osteoporosis were isolated from femoral heads after low-energy fracture of the femoral neck. Control cells were obtained from bone marrow of femoral heads of middle-aged, non-osteoporotic donors after total hip arthroplasty.
The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.
Sex, Age, Specimen part, Disease
View SamplesIn the present study we analyzed the effect of cellular senescence on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from bone marrow. Human MSC were isolated from femoral heads of non-osteoporotic donors after total hip arthroplasty.
The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.
Sex, Age, Specimen part
View SamplesIn the present study we analyzed the effect of primary osteoporosis on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from human bone marrow. Human MSC of elderly patients suffering from osteoporosis were isolated from femoral heads after low-energy fracture of the femoral neck. Bone marrow of age-matched, non-osteoporotic donors was obtained of femoral heads after total hip arthroplasty.
The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.
Sex, Age, Specimen part, Disease
View SamplesIn the present study we analyzed the effect of advanced donor age on the transcriptome of human mesenchymal stem cells (hMSC; alternatively named mesenchymal stromal cells) from bone marrow. Human MSC of elderly and middle-aged patients without symptoms of osteoporosis were isolated from femoral heads after total hip arthroplasty.
The transcriptional profile of mesenchymal stem cell populations in primary osteoporosis is distinct and shows overexpression of osteogenic inhibitors.
Sex, Age, Specimen part
View SamplesWe performed gene expression microarray comparing Osx-mCherry cells and Ocn-Topaz cells isolated from the OsxCre-mCherry;OcnCre-Topaz double transgenic mice by flow cytometry.
Specific bone cells produce DLL4 to generate thymus-seeding progenitors from bone marrow.
Specimen part
View SamplesSOX9 is generally not expressed in melanomas with a high proliferative capacity but is expressed in melanomas with a high invasive capacity. Here we overexpress full length SOX9 in M010817, a melanoma cell culture with high proliferative capacity but low invasive capacity.
Methylation-dependent SOX9 expression mediates invasion in human melanoma cells and is a negative prognostic factor in advanced melanoma.
Specimen part, Cell line
View SamplesThe precise makeup of chromatin remodeling complexes is important for determining cell type and cell function. The SWI/SNF chromatin remodeling complex is made up of multiple subunits that can be filled by mutually exclusive proteins. Inclusion or exclusion of these proteins has profound functional consequences, yet we currently understand little about the direct functional relationship between these biochemically distinct forms of remodeling complexes. Here we combine chromatin immunoprecipitation, transcriptome analysis, and transcription factor binding information from the ENCODE project to determine the functional relationship between three biochemically distinct forms of SWI/SNF. We find widespread overlap in transcriptional regulation and the genomic binding of the three ARID (AT-Rich Interacting Domain) subunits of SWI/SNF. Despite the numerous similarities in their transcriptional regulation and the co-factors bound with each ARID we identify several novel interaction modalities. Previous work has found examples of competition or subunit switching at individual loci, and we find this functional relationship is widespread, and in these cases gene expression changes following loss of one ARID depend on the function of another ARID. We also identify a previously unknown cooperative interaction between ARID1B and ARID2 in the repression of a large number of genes. Together these data help untangle the complicated combinatorial relationships between a highly heterogenous chromatin remodeling family. Overall design: We performed depletion of ARID subunits (ARID1A , n=5; ARID1B, n=3, ARID2, n=5) of SWI/SNF using siRNA or a Non-Targeting control (N=6) and performed expression analysis using polyA+ selected RNA and a strand-specific dUTP incorporation library protocol.
Genome-Wide Transcriptional Regulation Mediated by Biochemically Distinct SWI/SNF Complexes.
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View SamplesMicroglia are tissue macrophages of the central nervous system (CNS) that control tissue homeostasis, and as such they are crucially important for organ integrity. Microglia dysregulation is thought to be causal for a group of neuropsychiatric, neurodegenerative and neuroinflammatory diseases, called microgliopathies. However, how the intracellular stimulation machinery in microglia is controlled is poorly understood. By using expression studies, we identified the ubiquitin-specific protease (Usp) 18 in white matter microglia that essentially contributes to microglial quiescence under homeostatic conditions. We further found that microglial Usp18 negatively regulated the activation of STAT1 and concomitant induction of interferon-induced genes thereby disabling the termination of IFN signalling. Unexpectedly, the Usp18-mediated feedback loop was independent from the catalytic domain of the protease but instead required the interacting region of Ifnar2. Additionally, the absence of Ifnar1 completely rescued microglial activation indicating a tonic IFN signal mediated by receptor interactions under non-diseased conditions. Finally, conditional depletion of Usp18 only in myeloid cells significantly enhanced the disease burden in a mouse model of CNS autoimmunity, increased axonal and myelin damage and determined the spatial distributions of CNS lesions that shared the same STAT1 signature as myeloid cells found in active multiple sclerosis (MS) lesions. These results identify Usp18 as novel negative regulator of microglia activation, demonstrate a protective role of the IFNAR pathway for microglia and establish Usp18 as potential therapeutic target for the treatment of MS.
USP18 lack in microglia causes destructive interferonopathy of the mouse brain.
Specimen part
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