Loss of one allele of Ebf1 impairs pre-B cell (B220+CD19+CD43low/negIgM-) expansion. In order to better understand the underlying cause of the reduced pre-B cell compartment in Ebf1+/- mice, we sorted pro-B (B220+CD19+CD43highIgM- ) as well as pre-B cells from Wt and Ebf1 heterozygote mutant mice and performed Affymetrix based microarray gene expression analysis.
Early B-cell factor 1 regulates the expansion of B-cell progenitors in a dose-dependent manner.
Specimen part
View SamplesEbf1 is a transcription factor with documented, and dose dependent, functions in both normal and malignant B-lymphocyte development. In order to understand more about the role of Ebf1 in malignant transformation, we have investigated the impact of reduced functional Ebf1 dose on early B-cell progenitors. Gene expression analysis in loss and gain of function analysis suggested that Ebf1 was involved in the regulation of genes of importance for DNA repair as well as cell survival. Investigation of the level of DNA damage in steady state as well as after induction of DNA damage by UV light supported that pro-B cells lacking one functional allele of Ebf1 display a reduced ability to repair DNA damage. This was correlated to a reduction in expression of Rad51 and combined analysis of published 4C and chromatin Immuno precipitation data suggested that this gene is a direct target for Ebf1. Even though the lack of one allele of Ebf1 did not result in any dramatic increase of tumor formation, we noted a dramatic increase in the formation of pro-B cell leukemia in mice carrying a combined heterozygote mutation in the Ebf1 and Pax5 genes. Even though the tumors were phenotypically similar and stable, we noted a large degree of molecular heterogeneity well in line with a mechanism involving impaired DNA repair. Our data support the idea that Ebf1 controls homologous DNA repair in a dose dependent manner and that this may explain the frequent involvement of Ebf1 in human leukemia
Ebf1 heterozygosity results in increased DNA damage in pro-B cells and their synergistic transformation by Pax5 haploinsufficiency.
Specimen part, Cell line, Time
View SamplesBackground: Niemann-Pick type C is a rare autosomal recessive lysosomal storage disorder presenting aggravating neurologic symptoms due degeneration of specific types of CNS neurons. At present, it is not well understood how neurons react to NPC1 deficiency and why some neuronal cell types are more vulnerable than others. Purpose: We took aimed to uncover how a specific type of CNS neuron that can be highly purified reacts to NPC1 deficiency based on changes in gene expression. Methods: Retinal ganglion cells were purified from individual one-week old Balb/c mice homozygous for a mutant NPC1 allele (NPC1m1N) and wildtype littermates (n = 4 mice each genotype) using immunopanning. Total RNA was isolated from acutely isolated neurons and subjected to RNAseq using 4 biological replicates for each genotype. Results: Our analysis revealed a strong downregulation of transcripts known to be decreased in mutant mice including Npc1 and Calb1 thus validating our approach. We observed a strong upregulation of genes for cellular cholesterol accretion and the downregulation of those for cholesterol release. Other changes including downregulation genes involved in the immune response and synaptic components. Conclusions: The observed changes suggest that neurons already at one week of age sense a cholesterol deficit because lipids accumulate in the endosomal-lysosomal system and cannot be redistributed intracellularly. Overall design: Gene expression analysis by RNAseq in retinal ganglion cells acutely purified from eight-days-old NPC1-deficient mice and wildtype littermates
Reversal of Pathologic Lipid Accumulation in NPC1-Deficient Neurons by Drug-Promoted Release of LAMP1-Coated Lamellar Inclusions.
Subject
View SamplesAt mid-log phase (OD600 of 0.5), unique gene expression patterns were observed between these two strains with 3.4% of the transcripts (188/5570) expressed differentially.
A novel oxidized low-density lipoprotein-binding protein from Pseudomonas aeruginosa.
No sample metadata fields
View SamplesInitiated hepatocytes (IHCs), isolated from DEN exposed Tgfbr2 flox/flox mouse, were infected with GFP or Cre-expressed adenovirus, followed by 1ng/ml TGFß × 48 hours incubation. Then total RNAs were isolated and processed to routine sequencing on Illumina platform. RNA-Seq libraries were prepared from total RNA using polyA enrichment. Overall design: Examination of transcriptome differences between initiated hepatocytes with or without Tgfbr2 inactivation.
A Transforming Growth Factor-β and H19 Signaling Axis in Tumor-Initiating Hepatocytes That Regulates Hepatic Carcinogenesis.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target.
Specimen part, Cell line
View Samplesin this study we define an epigenomic profile of PRC2 (H3K27me3 and bivalent) tragets in four newly diagnosed MM patients. Using Oncomine database we demonstarte that PRC2 targets are underexpressed with advanced ISS stages and correlated to poor outcome. Pharmacological inhibition of UNC1999 showed anti-myeloma potential in vitro by activating the expression genes related to apoptosis and cell differenatiation.
Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target.
Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.
Cell line
View SamplesTransgenic (Tg) mice expressing nuclear or cytoplasmic human TDP-43 were generated.
Dysregulation of the ALS-associated gene TDP-43 leads to neuronal death and degeneration in mice.
Sex
View SamplesWithin the overall project, we performed a set of microarray and chromatin-immunoprecipitation (ChIP)-chip experiments using siRNA against the (pro)renin receptor ((P)RR), stable overexpression of PLZF, the PLZF translocation inhibitor genistein and the specific V-ATPase inhibitor bafilomycin to dissect transcriptional pathways downstream of the (P)RR.
Distinct signal transduction pathways downstream of the (P)RR revealed by microarray and ChIP-chip analyses.
Cell line
View Samples