Comparison of transcriptome between wild type, CD4 cre conditional knock-out and Bcl11b mutant mice. Overall design: Five replicates from wt newborn thymus, three replicates mutant new born thymus and four replicate of Bcl11bfl/fl: Cd4-Cre mice.
Priming of lineage-specifying genes by Bcl11b is required for lineage choice in post-selection thymocytes.
Specimen part, Cell line, Subject
View SamplesRearrangements involving the NUP98 gene resulting in fusions to several partner genes occur in acute myeloid leukemia and myelodysplastic syndromes. This study demonstrates that the second FG repeat domain of the NUP98 moiety of the NUP98-HOXA9 fusion protein is important for its cell immortalization and leukemogenesis activities. We demonstrate that NUP98-HOXA9 interacts with MLL via this FG repeat domain and that, in the absence of MLL, NUP98-HOXA9-induced cell immortalization and leukemogenesis are severely inhibited. Molecular analyses indicate that MLL is important for the recruitment of NUP98-HOXA9 to the HOXA locus and for NUP98-HOXA9-induced HOXA gene expression. Our data indicate that MLL is crucial for NUP98-HOXA9 leukemia initiation.
MLL is essential for NUP98-HOXA9-induced leukemia.
No sample metadata fields
View SamplesRegeneration of fragmented Drosophila imaginal discs occurs in an epimorphic manner, involving local cell proliferation at the wound site. Following disc fragmentation, cells at the wound site activate a restoration program through wound healing, regenerative cell proliferation and repatterning of the tissue. However, the interplay of signaling cascades, driving these early reprogramming steps, is not well understood. Here we profiled the transcriptome of regenerating cells in the early phase within twenty-four hours after wounding. We found that JAK/STAT signaling becomes activated at the wound site and promotes regenerative cell proliferation in cooperation with Wingless (Wg) signaling. In addition, we demonstrated that the expression of Drosophila insulin-like peptide 8 (dilp8), which encodes a paracrine peptide to delay the onset of pupariation, is controlled by JAK/STAT signaling in early regenerating discs. Our findings suggest that JAK/STAT signaling plays a pivotal role in coordinating regenerative disc growth with organismal developmental timing.
During Drosophila disc regeneration, JAK/STAT coordinates cell proliferation with Dilp8-mediated developmental delay.
Sex, Specimen part, Treatment
View SamplesWe searched for roles of ZEB1 during EMT by RNA-seq in breast cancer cells. Overall design: Expression of mRNA in a basal type breast cancer cell line MDA-231-D transfected with ZEB1/ZEB2 siRNAs and stimulated with TGF-beta for 24 h.
ZEB1-regulated inflammatory phenotype in breast cancer cells.
Specimen part, Cell line, Subject
View SamplesDrosophila imaginal disc cells exhibit a remarkable ability to switch cell fates under various perturbations, a phenomenon known as transdetermination (TD). The winged eye (wge) gene induces eye-to-wing TD by its overexpression in eye imaginal discs using eye specific Gal4 driver (eyeless-Gal4). Gene network controlling this process, however, is largely unclear. Additionally, we identified that heterochromatin-related histone methyltransferase Su(var)3-9 is essential for wge-mediated TD.
winged eye Induces Transdetermination of Drosophila Imaginal Disc by Acting in Concert with a Histone Methyltransferase, Su(var)3-9.
Specimen part
View SamplesWe have analyzed publicly available K562 Hi-C data, which enables genome-wide unbiased capturing of chromatin interactions, using a Mixture Poisson Regression Model to define a highly specific set of interacting genomic regions. We integrated multiple ENCODE Consortium resources with the Hi-C data, using DNase-seq data and ChIP-seq data for 46 transcription factors and 8 histone modifications. We classified 12 different sets (clusters) of interacting loci that can be distinguished by their chromatin modifications and which can be categorized into three types of chromatin hubs. The different clusters of loci display very different relationships with transcription factor binding sites. As expected, many of the transcription factors show binding patterns specific to clusters composed of interacting loci that encompass promoters or enhancers. However, cluster 6, which is distinguished by marks of open chromatin but not by marks of active enhancers or promoters, was not bound by most transcription factors but was highly enriched for 3 transcription factors (GATA1, GATA2, and c-Jun) and 3 chromatin modifiers (BRG1, INI1, and SIRT6). To validate the identification of the clusters and to dissect the impact of chromatin organization on gene regulation, we performed RNA-seq analyses before and after knockdown of GATA1 or GATA2. We found that knockdown of the GATA factors greatly alters the expression of genes within cluster 6. Our work, in combination with previous studies linking regulation by GATA factors with c-Jun and BRG1, provide genome-wide evidence that Hi-C data identifies sets of biologically relevant interacting loci. Overall design: RNA-seq of control, siGATA1 and siGATA2 K562 cells
Integration of Hi-C and ChIP-seq data reveals distinct types of chromatin linkages.
Cell line, Subject
View SamplesGlioblastomas show heterogeneous histological features. These distinct phenotypic states are thought to be associated with the presence of glioma stem cells (GSCs), which are highly tumorigenic and self-renewing sub-population of tumor cells that have different functional characteristics. To investigate gene expression including lncRNA (long non-coding RNA) in GSC, we have performed high-throughput RNA-sequencing (RNA-seq) experiment using Illumina GAIIx. Overall design: Profiles of gene expression including lncRNA in GSC were generated by RNA-seq using Illumina GAIIx.
Targeting the Notch-regulated non-coding RNA TUG1 for glioma treatment.
No sample metadata fields
View SamplesMany neural progenitor cells present in the fetus, but also in adult brain, which play a major role for the reproduction for healingin regeneration of neuronal cells, when differentiated cells are damaged. However, effects of radiation effect on undifferentiated neural progenitor cells remained unclear. The radiation doses of medical exposure, pollution by nuclear power plant accidents, and other exposure of workers; medical workers, airline crews, and astronaut have been focused. In this study, we report the effects of low- to middle- dose doses of radiation on cultured human neural progenitor cells (hNPC) differentiated derived from embryonic stem (ES) cells, which are partially compared with those of human umbilical vein endothelial cell (HUVEC).
Effects of Chronic Low-Dose Radiation on Human Neural Progenitor Cells.
Specimen part, 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 SamplesIn previous in vitro study, we reported potential mechanism of cholesterol-lowering effect of Lactobacillus brevis119-2 (119-2) isolated from turnip Tsuda kabu is due to incorporation of cholesterol into 119-2 cell. In this study, we analyzed serum cholesterol and hepatic gene expression of Sprague-Dawley (SD) rat fed diet containing cholesterol with or without 119-2 for 2 weeks, to evaluate the cholesterol-lowering effect of 119-2 in vivo. Serum cholesterol of SD rat fed diet with 119-2 significantly decreased compared to SD rat fed diet without 119-2, and both viable and dead 119-2 indicated the effect. The result of hepatic gene analysis using DNA microarray suggested that potential mechanism of the cholesterol-lowering effect of 119-2 in vivo is inhibiting the activity of 3-hydroxy-3-methylglutaryl-CoA reductase by Insig (insulin induced gene) that is endoplasmic reticulum membrane protein, and catabolizing cholesterol to bile acid by Cyp7a1 (cytochrome P450 a1) that is the rate-limiting enzyme in the synthesis of bile acid from cholesterol. In addition, we concluded feeding 119-2 decreased serum low density lipoprotein (LDL) cholesterol by overexpression of Ldlr (LDL receptor gene). On the other hand, feeding Lactobacillus acidophilus ATCC43121 (ATCC) increased high density lipoprotein (HDL) cholesterol by over expression of Abca1 (ATP binding cassette sub-family A member 1 gene) and Angplt3 (Angiopoietin-like 3). These results suggested that 119-2 decrease the risk of atherosclerosis by serum cholesterol-lowering effect and improving effect of fatty liver and the LH (LDL cholesterol / HDL cholesterol) ratio.
Effect of Lactobacillus brevis 119-2 isolated from Tsuda kabu red turnips on cholesterol levels in cholesterol-administered rats.
Sex, Age, Specimen part
View Samples