Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system in which macrophages and microglia play a central role. During active multiple sclerosis foamy macrophages and microglia, containing degenerated myelin, are abundantly found in demyelinated areas. Recent studies have described an altered macrophage phenotype after myelin internalization. However, by which mechanisms myelin affects the phenotype of macrophages and how this phenotype can influence lesion progression is unclear.
Myelin-derived lipids modulate macrophage activity by liver X receptor activation.
Specimen part, Treatment
View SamplesPurpose:To identify resistance mechanisms for the chemotherapeutic drug fludarabine in chronic lymphocytic leukemia (CLL), as innate and acquired resistance to fludarabine-based chemotherapy represents a major challenge for long-term disease control. Methods: We employed piggyBac transposon-mediated mutagenesis, combined with next-generation sequencing, to identify genes that confer resistance to fludarabine in a human CLL cell line. Results: RNA-seq profiling of fludarabine-resistant cells suggested deregulated MAPK signaling as involved in mediating drug resistance in CLL. Overall design: To address if the fludarabine-resistant HG3 cells were transcriptionally different at a global level compared to their parental cells, we performed RNA-sequencing of three pairs of HG3 pools
Transposon Mutagenesis Reveals Fludarabine Resistance Mechanisms in Chronic Lymphocytic Leukemia.
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Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.
Specimen part, Cell line
View SamplesGene-expression in siRNA treated U2OS and hTERT-RPE1 cells showed that CASP8AP2, NPAT and HINFP do not regulate expression of each other, and do not have any common target genes, except histones. Most histone genes are downregulated in U2OS cells following loss of CASP8AP2, NPAT or HINFP. In normal cells, highly-expressed histone genes were downregulated, albeit less than in tumor cells following loss of CASP8AP2. The p53 target genes were upregulated relatively late, clearly after the changes in expression of histone genes were observed.
Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.
Cell line
View SamplesThe ACBP knockout were created by targeted disruption of the gene in mice. The expression profiling was performed on liver tissue from ACBP-/- (KO) and +/+ (WT) mice at the age of 21 days, which in our study is the time immediately before weaning. The mice used for this experiment were taken directly away from their mother. Thus, having free access to chow and breast milk until sacrificed at 8-11am
Disruption of the acyl-CoA-binding protein gene delays hepatic adaptation to metabolic changes at weaning.
Specimen part
View SamplesTranscriptome analysis of RNAs extracted from 2 hour-TGF-b-treated or untreated LX-2 cells with or without STAT3 knockdown
Transforming Growth Factor-β (TGF-β) Directly Activates the JAK1-STAT3 Axis to Induce Hepatic Fibrosis in Coordination with the SMAD Pathway.
Treatment, Time
View SamplesMouse hair follicles undergo synchronized cycles. Cyclical regeneration and hair growth is fueled by stem cells (SCs). Following hair regeneration, SCs within the bulge and its vicinity (upper ORS which becomes the bulge for the next cycle) briefly self-renew to replenish expended SCs and ensure long-term tissue regeneration.
An RNA interference screen uncovers a new molecule in stem cell self-renewal and long-term regeneration.
Sex, Specimen part
View SamplesMesenchymal stromal cells (MSCs) are multipotent stem cells with potent immunosuppressive and trophic support functions. Although bone marrow is considered the golden standard to isolate classical MSCs (BM-MSC), MSC-like cells are currently also derived from other, more easily accessible extra-embryonic tissues such as the umbilical cord. In this study we compared the gene expression profile of human Wharton's jelly explant-derived MSC cultures with two adult MSC populations derived from bone marrow, namely BM-MSC and multipotent adult progenitor cells (MAPC).
Human Wharton's Jelly-Derived Stem Cells Display a Distinct Immunomodulatory and Proregenerative Transcriptional Signature Compared to Bone Marrow-Derived Stem Cells.
Specimen part
View SamplesGenome-wide RNAi screens in mice identified Ctnnb1 and Mllt6 as physiological regulators of HrasG12V-dependent epidermal hyperplasia. To probe the consequences of Ctnnb1 and Mllt6 on HrasG12V-dependent oncogenic growth, we examined how their depletion impacts gene expression in the HrasoncoX2 epidermis. We performed RNA-seq analysis of FACS-purified embryonic epidermal cells, followed by network analysis of differentially regulated transcripts. Whether Ctnnb1 or Mllt6, knockdown markedly enhanced activity of genes restricting growth, and decreased expression of genes promoting epidermal proliferation. This contrasted with known transcriptional changes that typically follow epidermal expression of oncogenic Hras. Moreover, there was a significant overlap in genes whose expression was affected by Mllt6 and ß-catenin, further implying a level of shared function. Overall design: Transcriptional profiles of epidermal progenitors of embryonic day 18.5 animals of wild-type, HrasG12V, and HrasG12V depleted of Ctnnb1 or Mllt6 backgrounds.
RNAi screens in mice identify physiological regulators of oncogenic growth.
Cell line, Subject
View SamplesSW480 cells were treated with 2uM crizotinib for 72h (versus DMSO) Overall design: Examination of differential up- or down-regulated genes after crizotinib treatment
Global survey of the immunomodulatory potential of common drugs.
Cell line, Subject
View Samples