This SuperSeries is composed of the SubSeries listed below.
Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Specimen part
View SamplesDifferentiation of hematopoietic stem cells (HSCs) is regulated by a concert of different transcription factors (TFs). A disturbed function of TFs can be the basis of (pre)malignancies such as myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). Growth Factor Independence 1b (Gfi1b) is a repressing TF with a key role in quiescence of HSCs and emergence and maturation of erythrocytes and platelets. Here, we show that low expression of GFI1B in blast cells is associated with inferior prognosis of MDS and AML patients. Using mouse models with either reduced expression or conditional deletion of Gfi1b, crossed with a mouse model reflecting human MDS or AML, we demonstrate that AML development was accelerated with heterozygous loss of Gfi1b, and latency was further decreased when Gfi1b was conditionally deleted. Loss of Gfi1b significantly enhanced stemness of leukemic cells with upregulation of genes fundamentally involved in leukemia development. On a molecular level, we found that loss of Gfi1b not only increased the levels of reactive oxygen species (ROS) but also induced gene expression changes of key AML pathways such as the p38/AKT pathway. These results demonstrate that Gfi1b functions as an oncosuppressor in MDS/AML development.
Gfi1b: a key player in the genesis and maintenance of acute myeloid leukemia and myelodysplastic syndrome.
Specimen part
View SamplesMutations in the enzymes IDH1 and IDH2 have been identified in a wide variety of tumors like glioma, chondrosarcoma, thyroid cancer, lymphoma, melanoma, and in acute myeloid leukemia. Mutated IDH1/2 produces the metabolite 2-hydroxyglutarate (2HG), which interferes with epigenetic regulation of gene expression, and thus may promote tumorigenesis.
Pan-mutant-IDH1 inhibitor BAY1436032 is highly effective against human IDH1 mutant acute myeloid leukemia in vivo.
Specimen part, Treatment
View SamplesFiltered selection coupled with support vector machines generate functionally relevant prediction model for colorectal cancer. In this study, we built a model that uses Support Vector Machine (SVM) to classify cancer and normal samples using Affymetrix exon microarray data obtained from 90 samples of 48 patients diagnosed with CRC. From the 22,011 genes, we selected the 20, 30, 50, 100, 200, 300 and 500 genes most relevant to CRC using the Minimum-RedundancyMaximum-Relevance (mRMR) technique. With these gene sets, an SVM model was designed using four different kernel types (linear, polynomial, radial basis function and sigmoid).
Filtered selection coupled with support vector machines generate a functionally relevant prediction model for colorectal cancer.
Sex, Age, Specimen part, Disease stage
View SamplesTo investigate the effects of quality of fat in a high fat diet (HFD) over time on hepatic lipid storage and transcriptome in mice.
Eicosapentaenoic and docosahexaenoic acid-enriched high fat diet delays the development of fatty liver in mice.
Sex, Specimen part, Time
View SamplesIdentifying molecular effects between herring and beef diet in Ldlr-/- mice
Identifying molecular effects of diet through systems biology: influence of herring diet on sterol metabolism and protein turnover in mice.
Specimen part
View SamplesThe nuclear exosome performs critical functions in non-coding RNA processing, and in diverse surveillance functions including the quality control of mRNP formation, and in the removal of pervasive transcripts. Most non-coding RNAs and pervasive nascent transcripts are targeted by the Nrd1p-Nab3p-Sen1p (NNS) complex to terminate Pol II transcription coupled to nuclear exosome degradation or 3´-end trimming. Prior to nuclear exosome activity, the Trf4p-Air2p-Mtr4p polyadenylation complex adds an oligo-A tail to exosome substrates. Inactivating exosome activity stabilizes and lengthens these A-tails. We utilized high-throughput 3´-end poly(A)+ sequencing to identify at nucleotide resolution the 3´ ends targeted by the nuclear exosome, and determine the sites of NNS-dependent termination genome-wide. Overall design: 3´-end mapping of wild-type and various nuclear exosome mutant strains, either using gene knockouts or the anchor away system to conditionally deplete FRB-tagged proteins from the nucleus
Common genomic elements promote transcriptional and DNA replication roadblocks.
Subject
View SamplesWe generated gene expression profiles of N2 (wild type) and strain FAS43 (Histone H3.3 null worms containing knockout alleles of all genes with homology to human histone H3.3: his-69, his-70, his-71, his-72, his-74) at embryonic and first larval instar stages. Overall design: RNA was isolated from N2 and H3.3 null mixed-stage embryos and L1 larvae grown at 20°C using Trizol, in duplicates for all samples. RNA-seq libraries were prepared using the Illumina TruSeq protocol.
Differential Expression of Histone H3.3 Genes and Their Role in Modulating Temperature Stress Response in <i>Caenorhabditis elegans</i>.
Cell line, Subject
View SamplesMyeloid derived suppressor cells (MDSC) playing the immune suppressive roles in tumor bearing host consists of two major subsets of granulocytic and monocytic cells. Granulocytic MDSC (G-MDSC) express CD11b+ Gr-1high Ly6G+ Ly6Clow and produce high level of reactive oxygen species (ROS). Interestingly, neutrophils are well known ROS producing cells during immune defensive process and share same surface markers with G-MDSC. These similar features always brought the fundamental questions whats the difference between G-MDSC and neutrophils but its not yet proven clearly.
Characterization of the nature of granulocytic myeloid-derived suppressor cells in tumor-bearing mice.
Sex, Specimen part
View SamplesLamina propria and muscularis macrophages, were sorted at steady steate and 2h after oral exposure to an attenuated form of Salmonella, comparison among these populations showed that the muscularis macrophages quckly respond to the presence of intestinal bacteria, upregulating some important tissue protective genes. Overall design: intestinal macrophages from 3 mice were pooled into one RNA sample, the experiment was done control X infected and was repeated twice
Neuro-immune Interactions Drive Tissue Programming in Intestinal Macrophages.
Specimen part, Cell line, Subject
View Samples