Project description:The transcriptome of LT-HSC (CD34+CD38-CD45RA+CD90+CD49f+) and ST-HSC (CD34+CD38-CD45RA+CD90-CD49f-) from healthy adult human Bone Marrow Cells were assessed by RNA-seq.
Project description:Hybridization of diverged taxa often result in lethality or sterility. We previously described natural variation for postzygotic incompatibility in the cross of diploid Arabidopsis thaliana to Arabidopsis arenosa. Hybrid seed death in this system has a complex genetic basis, involving many non-additive interactions. While activation of AGAMOUS-LIKE genes (AGL) and Athila elements have been detected 5-8 days after pollination (DAP), the molecular basis of death remains mysterious. To address this problem, we compared 3DAP transcriptomes in interspecific hybrids from two A. thaliana ecotypes, one compatible, the other incompatible. Relative to self crosses of the respective A. thaliana seed parent, hybrids displayed differential expression of key developmental regulators in both the endosperm and maternal seed coat as well as natural variation for stress response genes. Ribosomal protein genes and a photosynthetic cluster of genes were hyperactivated, presumably in response to growth signals. Suppressing endosperm growth factor IKU1 and defense response regulators such as NON-EXPRESSOR OF PATHOGENESIS RELATED1 (NPR1) improved hybrid seed survival. Therefore, in incompatible hybrids disruption of seed development most likely initiates in the endosperm, rapidly affecting embryo and seed coat. The activation of putative POLYCOMB REPRESSIVE COMPLEX (PRC) gene targets, together with a twenty-fold reduction in expression of the FERTILIZATION INDEPENDENT SEED 2 gene, indicates a PRC role. Examination of differential gene expression of incompatible A. thaliana eco. Col-0 X A. arenosa and compatible A. thaliana eco. C24 X A. arenosa hybrid seeds plus corresponding A. thaliana and A. arenosa control crosses.
Project description:Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequent in human glioblastomas1 and cytogenetically normal acute myeloid leukemias (AML)2. These alterations are gain-of-function mutations in that they drive the synthesis of the M-bM-^@M-^\oncometaboliteM-bM-^@M-^] R-2-hydroxyglutarate (2HG)3. It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukemogenesis. Here we report the characterization of conditional knock-in mice in which the most common IDH1 mutation, Idh1-R132H, is inserted into the endogenous murine Idh1 locus and is expressed in cells of the hematopoietic (Vav-KI) or more specifically in cells of the myeloid (LysM-KI) lineage. These mutants show increased numbers of early hematopoietic progenitors and develop splenomegaly and anemia with extramedullary hematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells exhibit both hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1/2-mutant AML. Thus, our study is the first to describe the generation of conditional Idh1-R132H-KI mice. Furthermore, our study is also the first report showing the induction of a leukemic DNA methylation signature in a modeled system and sheds light on the mechanistic links between IDH1 mutation and human AML. DNA methylation profiling in LSK cells from IDH1-R132H knock-in mice vs. control mice
Project description:RNA-seq of zebrafish embryos with mutations in srpk3 (sa1890 allele) and/or ttn.1 (sa5562 allele). Each of the 24 samples (six samples for each of four genotypes) represents RNA from a pool of three 5 dpf zebrafish embryos.
Project description:The C57BL/6J mouse model develops obesity and pre-diabetes when fed a high-fat diet. In this experiment, DNA methylation was assessed globally at specific CpG sites in liver tissue from mice receiving high-fat diet (45E% from fat) for 13 weeks (Control) or high-fat diet supplemented with 20% (w/w) of freeze-dried lingonberries (n=4). Our findings show that lingonberries prevent development of high-fat induced obesity, hepatic steatosis and low-grade inflammation, and the DNA was hypermethylated in mice receiving lingonberries compared to control. Genome wide hepatic DNA methylation comparison between mice fed high-fat diet with or without a lingonberry supplement (n=4/group).