Susceptibility genes for Autism Spectrum Disorder (ASD), Fragile X Syndrome (FXS), monogenetic disorders with intellectual disabilities (ID) or schizophrenia (SCZ) converge on processes related to neuronal function and differentiation. Furthermore, ASD risk genes are enriched for FMRP (Fragile X Mental Retardation Protein) targets and for genes implicated in ID. In addition, a significant co-heritability was observed between ASD and SCZ. The genetic overlap between ASD, FXS, ID and SCZ together with the symptomatic differences gives rise to the question if pathomechanisms impair the same or different regulatory patterns activated during neuronal differentiation (ND). To test this idea, we performed transcriptome analysis of in-vitro differentiation of the neuroblastoma cell line model SH-SY5Y and identified genes that were differentially expressed, dynamically regulated, and coordinately expressed. The identified genetic modules activated during ND are enriched for genetic risk factors for these four disorders. Although risk genes for the disorders significantly overlap, we observed disorder specific enrichments: ASD or FXS implicated genes were likely to be positive regulators of ND whereas ID implicated genes were related to negative regulation. ASD and SCZ genes were specifically enriched among cholesterol and fatty acid associated modules. ID genes were overrepresented among cell cycle modules. In addition, we show that ASD genes are likely to be hub genes. We hypothesize that knowledge about genetic variants of an individual combined with network and pathway context of the related genes will allow differentiating between psychiatric disorders.
Transcriptomic signatures of neuronal differentiation and their association with risk genes for autism spectrum and related neuropsychiatric disorders.
Sex, Specimen part, Cell line
View SamplesTranscriptome analysis of five population of Antigen Presenting Cells: inflammatory macrophages, Inflammatory dendritic cells, Cd14+CD16- monocytes, CD14 dim Cd16+ monocytes and BDCA1+ Dendritic cells.
Human inflammatory dendritic cells induce Th17 cell differentiation.
No sample metadata fields
View SamplesDespite substantial investments, tuberculosis remains one of the biggest challenges in public health.
Synergy of chemotherapy and immunotherapy revealed by a genome-scale analysis of murine tuberculosis.
Sex, Specimen part
View SamplesMounting evidence points to a link between a cancer possessing stem-like properties and a worse prognosis. To understand the biology, a common approach is to integrate network biology with signal processing mechanics. That said, even with the right tools, predicting the risk for a highly susceptible target using only a handful of gene signatures remains very difficult. By compiling the expression profiles of a panel of tumor stem-like cells (TSLCs) originating in different tissues, comparing these to their parental tumor cells (PTCs) and the human embryonic stem cells (hESCs), and integrating network analysis with signaling mechanics, we propose that network topologically-weighted signaling processing measurements under tissue-specific conditions can provide scalable and predicable target identification.
Network biology of tumor stem-like cells identified a regulatory role of CBX5 in lung cancer.
Specimen part
View SamplesFibrosis is a leading cause of deaths in industrialized countries and has no effective therapy. We demonstrated that blockade of OX40L prevented inflammation-driven fibrosis affecting the skin and the lungs and promotes regression of established dermal fibrosis in different murine models.
OX40L blockade protects against inflammation-driven fibrosis.
Sex, Age, Specimen part, Treatment
View SamplesHistone deacetylase 1 (HDAC1) is an enzyme that promotes deacetylation of acetylated lysine residues in histones and other proteins. Histone acetylation is often associated with gene activation and expression. Los of HDAC1 leads to severe problems in development and proliferation. Moreover, it seems to be the major histone deacetylase in mouse embryonic stem cells.
Negative and positive regulation of gene expression by mouse histone deacetylase 1.
No sample metadata fields
View SamplesPrevious reports have defined three subsets of mouse NK cells on the basis of the expression of CD27 and CD11b. The developmental relationship between these subsets was unclear. To address this issue, we evaluated the overall proximity between mouse NK cell subsets defined by CD27 and CD11b expression using pangenomic gene expression profiling. The results suggest that CD27+CD11b-, CD27+CD11b+ and CD27-CD11b+ correspond to three different intermediates stages of NK cell development.
Maturation of mouse NK cells is a 4-stage developmental program.
No sample metadata fields
View SamplesThe objective of this study is to determine how inhibition of microRNA 10b affects gene expression in neurospheres cultures of glioblastoma stem-like cells.
Therapeutic potential of targeting microRNA-10b in established intracranial glioblastoma: first steps toward the clinic.
Treatment
View SamplesRetinal ganglion cells (RGCs) and retinal pigment epithelium (RPE) cells are two retinal cell types that are affected by the most prevalent retinal diseases leading to irreversible blindness, such as glaucoma affecting the former and age-related macular degeneration affecting the latter. One of the most promising approaches for the therapy of these diseases is via the autologous transplantation of RGC or RPE cells derived from the induced pluripotent stem cells (iPSCs). This emphasizes the importance of detailed characterization and understanding of the mechanisms of differentiation of iPSCs into retinal lineages on the genome-wide scale. Such information can be used to identify novel crucial regulators of differentiation, optimisation of differentiation protocols to make them more efficient and safe, identification of novel specific biomarker signatures of differentiated cells. In this study, we performed the genome-wide transcriptome analysis of terminally differentiated RGC and RPE lineages, as well as intermediate retinal progenitor cells (RPCs) of optic vesicles (OVs) derived from the human induced pluripotent stem cells (iPSCs). In our analysis we specifically focused on the classes of transcripts that encode regulators of gene expression, such as transcription factors, epigenetic factors, and components of signaling pathways.
Expression profiling of cell-intrinsic regulators in the process of differentiation of human iPSCs into retinal lineages.
Specimen part
View SamplesPompe disease is caused by autosomal recessive mutations in the GAA gene, which encodes acid alpha-glucosidase. Although enzyme replacement therapy has recently improved patient survival greatly, the results in skeletal muscles and for advanced disease are still not satisfactory. Here, we report the derivation of Pompe disease induced pluripotent stem cells (PomD-iPSCs) and their potential for pathogenesis modeling, drug testing and disease marker identification. PomD-iPSCs maintained pluripotent features, and had low GAA activity and high glycogen content. Cardiomyocyte-like cells (CMLCs) differentiated from PomD-iPSCs recapitulated the hallmark Pompe disease pathophysiological phenotypes, including high levels of glycogen, abundant intracellular LAMP-1- or LC3-positive granules, and multiple ultrastructural aberrances. Drug rescue assessment showed that exposure of PomD-iPSC-derived CMLCs to rhGAA reversed the major pathologic phenotypes. Further, L-carnitine and 3- methyladenine treatment reduced defective cellular respiration and buildup of phagolysosomes, respectively, in the diseased cells. By comparative transcriptome analysis, we identified glycogen metabolism, lysosome and mitochondria related marker genes whose expression robustly correlated with the therapeutic effect of drug treatment in PomD-iPSC-derived CMLCs. Collectively, these results demonstrate that PomD-iPSCs are a promising in vitro disease model for development of novel therapeutic strategies for Pompe disease.
Human Pompe disease-induced pluripotent stem cells for pathogenesis modeling, drug testing and disease marker identification.
Specimen part
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