To characterize LICs in ALL irrespective of surface markers expression, we investigated leukemia initiating activities of cellular subfractions of patient-derived xenograft BCP-ALL cells sorted according to different cell cycle phases (i.e. G0/G1 and G2/M) followed by transplantation onto NOD/SCID mice. All cell fractions led to leukemia engraftment indicating LIC activity irrespective of cell cycle stage. Most importantly, cells isolated from G0/G1 cell cycle phases led to early leukemia engraftment in contrast to cells from late cell cycle (G2/M). To further characterize cells with different engraftment potential in vivo, we analyzed the gene expression profiles of early (G1b early) and late (G2/M) engrafting cells.
Leukemia reconstitution <i>in vivo</i> is driven by cells in early cell cycle and low metabolic state.
Specimen part
View SamplesCNS leukemia is still the major obstacle in treating childhood acute lymphoblastic leukemia (ALL). We have used our NOD/SCID/huALL xenotransplantation model to identify molecular pathways leading to the infiltration of leukemic cells into the CNS compartment.
Central nervous system involvement in acute lymphoblastic leukemia is mediated by vascular endothelial growth factor.
No sample metadata fields
View SamplesWe found that small moleculal weight FOXO1 inhibitor has antitumor affect against BCP-ALL cell lines RS4;11 and UoCB6
Tight regulation of FOXO1 is essential for maintenance of B-cell precursor acute lymphoblastic leukemia.
Cell line
View SamplesOligodendrocytes (OLs) and myelin are critical for normal brain function and they have been implicated in neurodegeneration. Human neuroimaging studies have demonstrated that alterations in axons and myelin occur early in Alzheimer's Disease (AD) course. However, the molecular mechanism underlying the role of OLs in AD remains largely unknown. In this study, we systematically interrogated OL-enriched gene networks constructed from large-scale genomic, transcriptomic, and proteomic data in human AD postmortem brain samples. These robust OL networks were highly enriched for genes associated with AD risk variants, including BIN1. We corroborated the structure of the AD OL coexpression and gene-gene interaction networks through ablation of genes identified as key drivers of the networks, including UGT8, CNP, MYRF, PLP1, NPC1, and NDGR1. Perturbations of these key drivers not only caused dysregulation in their associated network neighborhoods, but also mimicked pathways of gene expression dysregulation seen in human AD postmortem brain samples. In particular, the OL subnetwork controlled by the AD risk gene PSEN1 was strongly dysregulated in AD, suggesting a potential role of PSEN1 in disrupting the myelination pathway towards the onset of AD. In summary, this study built and systematically validated the first comprehensive molecular blueprint of OL dysregulation in AD, and identified key OL- and myelination-related genes and networks as potential candidate targets for the future development of AD therapies. Overall design: The mouse knockout models have been previously described for each of Ugt8 (Coetzee et al., 1996), Cnp (Lappe-Siefke et al., 2003), and Plp1 (Klugmann et al., 1997). For each of the two conditions studied (control and homozygous knockout mice), five mice of either sex were sacrificed at postnatal day 20 and brains were flashed-frozen until analysis. The frontal cortex (FC) and cerebellum (CBM) were dissected out and individually processed. RNA was isolated using Trizol reagent and processed using Ribo-Zero rRNA removal. RNA-sequencing was performed using the Illumina HiSeq2000 with 100 nucleotide paired-end reads. RNA-sequencing reads were mapped to the mouse genome (mm10, UCSC assembly) using Bowtie (version 2.2.3.0), TopHat (version 2.0.11), and SamTools (version 0.1.19.0) using a read length of 100. Reads were converted to counts at the gene level using HTSeq on the BAM files from TopHat2 using the UCSC known genes data set.
Multiscale network modeling of oligodendrocytes reveals molecular components of myelin dysregulation in Alzheimer's disease.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia.
Age, Specimen part, Time
View SamplesPurpose: The goal of this study was to assess gene expression changes upon SAHA treatment in neurons derived from patients with A152T Tau mutation Overall design: iPSC derived neurons were treated with SAHA at different dosage for several days
Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia.
No sample metadata fields
View SamplesPurpose: The goal of this study was to assess gene expression changes upon SAHA treatment in cells overexpressing miR-203. Overall design: Primary cortical cultures were established using E15 cortical cultures from C57BL/6J mice. At DIV0, cells were infectd with either miR-203 (high titre - 1MOI) or intermediate titre (0.5MOI) or control (high 1MOI) lentivirus andalso treated with different dose of SAHA. At DIV8, total RNA was isolated using NucleoSpin RNA XS kit (Takara). Libraries were prepared using Standard illumina stranded mRNA-seq protocol.
Identification of evolutionarily conserved gene networks mediating neurodegenerative dementia.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Differential gene expression profiles are dependent upon method of peripheral blood collection and RNA isolation.
No sample metadata fields
View SamplesRNA isolation and purification steps greatly influence the results of gene expression profiling. There are two commercially available products for whole blood RNA collection, PAXgene and Tempus blood collection tubes, and each comes with their own RNA purification method. We examined the impact of RNA isolation methods on gene expression profiles.
Differential gene expression profiles are dependent upon method of peripheral blood collection and RNA isolation.
No sample metadata fields
View SamplesBackground: Udder infections with environmental pathogens like Escherichia coli are a serious problem for the diary industry. Reduction of incidence and severity of mastitis is desirable and mild priming of the immune system either through vaccination or with low doses of an immune stimulant like lipopolysaccharide LPS was previously found to dampen detrimental effects of a subsequent infection. Monocytes / macrophages are known to develop tolerance to the endotoxin (ET) LPS as adaptation strategy to prevent exuberant inflammation. We have recently observed that application of 1 g of LPS/udder quarter effectively protects the cow for several days from an experimentally elicited mastitis. We have modelled this process in primary cultures of Mammary Epithelial Cells (MEC) from the cow. This is by far the most abundant cell type in the udder coming into contact with invading pathogens and little is known about the role of MEC in establishing ET in the udder.
Lipopolysaccharide priming enhances expression of effectors of immune defence while decreasing expression of pro-inflammatory cytokines in mammary epithelia cells from cows.
Specimen part, Time
View Samples