One and four month formalin-fixed paraffin embedded biopsies from 48 kidney transplant recipients (24 AKI donors, 24 non-AKI) underwent global gene expression profiling using DNA microarrays (96 arrays). At one month, there were 898 differentially expressed genes in the AKI group (p-value <0.005; FDR <10%), but by 4-months there were no longer any differences.
Transplanting Kidneys from Deceased Donors With Severe Acute Kidney Injury.
No sample metadata fields
View SamplesIn this study, we used a cross-species network approach to uncover nitrogen (N)-regulated network modules conserved across a model and a crop species. By translating gene network knowledge from the data-rich model Arabidopsis (Arabidopsis thaliana, ecotype Columbia-0) to a crop, rice (Oryza sativa spp. japonica (Nipponbare)), we identified evolutionarily conserved N-regulatory modules as targets for translational studies to improve N use efficiency in transgenic plants.
Cross-Species Network Analysis Uncovers Conserved Nitrogen-Regulated Network Modules in Rice.
Age, Specimen part
View SamplesNitrogen and light are two major regulators of plant metabolism and development. While genes involved in the control of each of these signals have begun to be identified, regulators that integrate gene responses to nitrogen and light signals have yet to be determined.
Modeling the global effect of the basic-leucine zipper transcription factor 1 (bZIP1) on nitrogen and light regulation in Arabidopsis.
Specimen part
View SamplesThis microarray experiment serves to identify the genes in the Arabidopsis genome that are regulated by carbon and light signaling interactions in 7 day dark grown seedlings. The expression profile of wild-type will be compared to the cli186 mutant, a mutant defective in carbon and light signaling. Plants of both the wild-type and cli186 genotypes are treated with the following light (L) and carbon (C) treatments: -C-L, +C-L, +C+L, -C+L. Comparison of the expression profiles under all treatments will help to identify genes that are misregulated in carbon and/or light treatments in the cli186 mutant.
An integrated genetic, genomic and systems approach defines gene networks regulated by the interaction of light and carbon signaling pathways in Arabidopsis.
Age
View SamplesHistone methylation modulates gene expression in response to external and internal cues. We uncovered a non-redundant role for the Arabidopsis histone methyltransferase, SDG8, which provides a unique opportunity to study the global function of a specific histone methyltransferase within in a multicellular organism. We previously used a promoter responsive to light and carbon in a positive genetic screen to identify an Arabidopsis carbon and light insensitive mutant cli186. In this study, we characterize the mutant cli186 as a complete deletion of a histone methyltransferase gene SDG8 (now renamed sdg8-5). To assess the global role of SDG8, we compared the global histone methylation patterns and the transcriptome of sdg8-5 to wild type (WT) in the context of a transient carbon and light treatment. We showed that the complete deletion of SDG8 in sdg8-5 is associated with a dramatic reduction of H3K36me3 towards the 3 of the gene body, which correlates with significant reduction in gene expression. We uncovered 1,084 high confidence functional targets of SDG8 affected in both H3K36me3 marks and gene expression that are associated with specific biological processes including defense, photosynthesis, nutrient metabolism and energy metabolism. Importantly, 71% of these functional targets are responsive to carbon and/or light. Our model suggests that SDG8 functions to mark specific sets of genes with H3K36me3 in the gene body for active transcription, to tune genes involved in primary metabolism that are responsive to the energy level in the environment.
The histone methyltransferase SDG8 mediates the epigenetic modification of light and carbon responsive genes in plants.
Treatment
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 SamplesWe found that a H3K4 specific histone methyltransferase MLL1, a mammalian homologue of Drosophila trithorax, is essential for circadian transcription. MLL1 is in a complex with CLOCK:BMAL1 and contributes to their rhythmic recruitment to circadian promoters and cyclic H3K4 tri-metylation. To analyze the function of MLL1 on circadian gene regulation, we performed comparative microarray analysis of global gene expression levels in WT and MLL1-deficient MEF, at two different circadian time points (CT18 and CT30). This analysis identified several genes whose expression levels were remarkably changed between CT18 and CT30 in WT and MLL1-KO MEF. Typical clock-regulated genes such as Per2, Per3, Bmal1, or Dbp were found to be changing in WT but not in MLL1-KO MEFs.
The histone methyltransferase MLL1 permits the oscillation of circadian gene expression.
Specimen part, Time
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 SamplesPartial induced pluripotent cells (iPSCs) are cell lines strayed from normal route from somatic cells to iPSCs and are immortalized. Mouse partial iPSCs are able to convert to real iPSCs by the exposure to 2i condition using MAPK and GSK3? inhibitors. However, the molecular mechanisms of this conversion are totally not known. Our piggyback vector mediated genome-wide screen revealed that Cnot2, one of core components of Ccr4-Not complex participates in this conversion. Subsequent analyses revealed other core components, i.e., Cnot1 and Cnot3 and Trim28 which is known to extensively share genomic binding sites with Cnot3 contribute to this conversion as well. Our bioinformatics analyses indicate that the major role of these factors in the conversion is the down-regulation of developmental genes in partial iPSCs.
Identification of Ccr4-not complex components as regulators of transition from partial to genuine induced pluripotent stem cells.
Sex, Specimen part
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
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