This SuperSeries is composed of the SubSeries listed below.
Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy.
Treatment
View SamplesThe role of the histone mehyltrasferase G9a (also known as Ehmt2) in cardiac hypertrophy has not been studied extensively. To address how G9a promotes cardiac hypertrophy, we assessed the gene expression signature defined by G9a in cardiomyocytes (CM) of mice subject to transverse aortic constriction (TAC) for 1 wk, a surgical procedure that causes cardiac hypertrophy following the induction of pressure overload. To this end, we compared the expression profiles of CMs isolated from mice treated with the G9a inhibitor BIX-01294 and control groups (untreated and DMSO-treated mice at baseline and after TAC). The expression profiles were defined by Illumina arrays .
Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy.
No sample metadata fields
View SamplesThe role of the histone mehyltrasferase G9a (also known as Ehmt2) in heart has not been extensively studied. To identify the genes regulated by G9a in the normal heart, we first generated a conditional, cardiac-specific KO mouse for this gene using the Cre-Lox approach, crossing G9a flox/flox mice with aMHC-MerCreMer mice (Cre mice were used as controls). Then, we sequenced total RNA (Total-RNA-seq) from cardiomyocyte-enriched populations isolated from G9a-KO and Cre mice, and compared the two expression profiles. Overall design: Profiling of the transcriptome of cardiomyocyte-enriched populations isolated from G9a-KO and Cre mice. Two biological replicates were profiled for each cell type.
Histone Methyltransferase G9a Is Required for Cardiomyocyte Homeostasis and Hypertrophy.
Cell line, Subject
View SamplesExtracellular nucleotides are potent signaling molecules mediating cell-specific biological functions. We previously demonstrated that adenosine 5'-triphosphate (ATP) inhibits the proliferation while stimulating the migration, in vitro and in vivo, of human bone marrow-derived mesenchymal stem cells (BM-hMSC). Here, we investigated the effects of ATP on BM-hMSC differentiation capacity.
Extracellular purines promote the differentiation of human bone marrow-derived mesenchymal stem cells to the osteogenic and adipogenic lineages.
Specimen part, Treatment, Time
View SamplesIn the present study, we investigated whether, and to what extent, P2Rs and their ligands are involved in the regulation of AML cells. Our findings show that AML blasts express several receptors belonging to the P2X and P2Y family. Although different samples respond differently to ATP and UTP stimulation (reflecting the variability intrinsic to the group of acute myeloid leukemias), all the tested samples appear to be responsive to purinergic signalling, as demonstrated by intracellular calcium mobilization.
Purinergic signaling inhibits human acute myeloblastic leukemia cell proliferation, migration, and engraftment in immunodeficient mice.
Specimen part
View SamplesWe show the molecular and functional characterization of a novel population of lineage-negative CD34-negative (Lin- CD34-) hematopoietic stem cells (HSCs) from chronic myelogenous leukemia (CML) patients at diagnosis. Molecular caryotyping and quantitative analysis of BCR/ABL transcript demonstrated that about one third of CD34- was leukemic. CML CD34- cells showed kinetic quiescence and limited clonogenic capacity. However, stroma-dependent cultures and cytokines induced CD34 expression on some HSCs, cell cycling, acquisition of clonogenic activity and increased expression of BCR/ABL transcript. CML CD34- cells showed an engraftment rate in immunodeficient mice similar to that of CD34+ cells. Gene expression profiling revealed the down-regulation of cell cycle arrest genes together with genes involved in antigen presentation and processing, while the expression of angiogenic factors was strongly up-regulated when compared to normal counterparts. Flow cytometry analysis confirmed the significant down-regulation of HLA class I and II molecules in CML CD34-cells. Increasing doses of imatinib mesilate (IM) did not affect fusion transcript levels, BCR-ABL kinase activity and the clonogenic efficiency of CML CD34- cells as compared to leukemic CD34+cells.
Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34- cell population with intrinsic resistance to imatinib.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Polycomb function during oogenesis is required for mouse embryonic development.
Specimen part, Treatment
View SamplesIn mammals, totipotent pre-implantation embryos are formed by fusion of highly differentiated oocytes and spermatozoa. Acquisition of totipotency concurs with remodeling of chromatin states of parental genomes (epigenetic reprogramming), changes in maternally contributed transcriptome and proteome, and zygotic genome activation. Genomes of mature germ cells are more proficient in supporting embryonic development than those of somatic cells. It is currently unknown whether transgenerational inheritance of chromatin states present in mature gametes underlies the efficacy of early embryonic development after natural conception. Here, we show that Ring1 and Rnf2, two core components of the Polycomb Repressive Complex 1 (PRC1), serve redundant gene regulatory functions during oogenesis that are required to support embryonic development beyond the two-cell stage. Numerous developmental regulatory genes that are established Polycomb targets in various somatic cell types are de-repressed in Ring1/Rnf2 double mutant (dm) fully grown germinal vesicle (GV) oocytes. Translation of tested aberrant maternal transcripts is, however, delayed until after fertilization. Exchange of maternal pro-nuclei between control and Ring1/Rnf2 maternally dm early zygotes demonstrates an essential role for Ring1 and Rnf2 during oogenesis in defining cytoplasmic and nuclear maternal contributions that are both essential for proper initiation of embryonic development. A large number of genes up-regulated in Ring1/Rnf2 dm GV oocytes harbor PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) in spermatozoa and in embryonic stem cells (ESCs), and are repressed during normal oogenesis and early embryogenesis. These data strongly support the model that Polycomb acts in the female and male germline to silence differentiation inducing genes and to program chromatin states, thereby sustaining developmental potential across generations.
Polycomb function during oogenesis is required for mouse embryonic development.
Specimen part
View SamplesIn mammals, totipotent pre-implantation embryos are formed by fusion of highly differentiated oocytes and spermatozoa. Acquisition of totipotency concurs with remodeling of chromatin states of parental genomes (epigenetic reprogramming), changes in maternally contributed transcriptome and proteome, and zygotic genome activation. Genomes of mature germ cells are more proficient in supporting embryonic development than those of somatic cells. It is currently unknown whether transgenerational inheritance of chromatin states present in mature gametes underlies the efficacy of early embryonic development after natural conception. Here, we show that Ring1 and Rnf2, two core components of the Polycomb Repressive Complex 1 (PRC1), serve redundant gene regulatory functions during oogenesis that are required to support embryonic development beyond the two-cell stage. Numerous developmental regulatory genes that are established Polycomb targets in various somatic cell types are de-repressed in Ring1/Rnf2 double mutant (dm) fully grown germinal vesicle (GV) oocytes. Translation of tested aberrant maternal transcripts is, however, delayed until after fertilization. Exchange of maternal pro-nuclei between control and Ring1/Rnf2 maternally dm early zygotes demonstrates an essential role for Ring1 and Rnf2 during oogenesis in defining cytoplasmic and nuclear maternal contributions that are both essential for proper initiation of embryonic development. A large number of genes up-regulated in Ring1/Rnf2 dm GV oocytes harbor PRC2-mediated histone H3 lysine 27 trimethylation (H3K27me3) in spermatozoa and in embryonic stem cells (ESCs), and are repressed during normal oogenesis and early embryogenesis. These data strongly support the model that Polycomb acts in the female and male germline to silence differentiation inducing genes and to program chromatin states, thereby sustaining developmental potential across generations.
Polycomb function during oogenesis is required for mouse embryonic development.
Treatment
View SamplesAstrocytes from optic nerve head from donors with and without glaucoma
Differential gene expression in astrocytes from human normal and glaucomatous optic nerve head analyzed by cDNA microarray.
No sample metadata fields
View Samples