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GSE13874
Mus musculus
14 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Calcium signaling is a central regulator of cardiomyocyte growth and function. Calmodulin is a critical mediator of calcium signals. Because the amount of calmodulin within cardiomyocytes is limiting, precise regulation of calmodulin expression may be an important for regulation of calcium signaling. In this study, we show for the first time that calmodulin levels are regulated post-transcriptionally in heart failure. The cardiomyocyte-restricted microRNA miR-1 inhibited translation of calmodulin-encoding mRNAs via highly conserved target sites within their 3-untranslated regions. In keeping with its effect on calmodulin expression, miR-1 downregulated calcium-calmodulin signaling through the calcineurin to NFAT. miR-1 also negatively regulated expression of Mef2a and Gata4, key transcription factors that mediate calcium-dependent changes in gene expression. Consistent with downregulation of these hypertrophy-associated genes, miR-1 attenuated cardiomyocyte hypertrophy in cultured neonatal rat cardiomyocytes and in the intact adult heart. Our data indicate that miR-1 regulates cardiomyocyte growth responses by negatively regulating the calcium-signaling components calmodulin, Mef2a, and Gata4.
Publication Title
MicroRNA-1 negatively regulates expression of the hypertrophy-associated calmodulin and Mef2a genes.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
Total RNAs were cloned from wt, Dis3L2 and Tailor mutant testis tissues to study the role of Tailor and Dis3L2 TUTase/nuclease complex Overall design: Replicated total RNA samples from Dis3L2 and Tailor single mutant, and Dis3L2/Tailor double mutant and WT (w1118) testes
Publication Title
Characterization of a TUTase/RNase complex required for <i>Drosophila</i> gametogenesis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 278 Downloadable Samples
- Illumina HiSeq 2500
Description
Aging is associated with functional decline of hematopoietic stem cells (HSC) as well as an increased risk of myeloid malignancies. We performed an integrative characterization of epigenomic and transcriptomic changes, including single-cell RNA-seq, during normal human aging. Lineage-CD34+CD38- cells (HSC-enriched, HSCe) undergo age-associated epigenetic reprogramming consisting of redistribution of DNA methylation and reductions in H3K27ac, H3K4me1 and H3K4me3. This reprogramming of aged HSCe globally targets developmental and cancer pathways which are comparably altered in AML of all ages; encompassing loss of 4,656 active enhancers, 3,091 bivalent promoters, and deregulation of several epigenetic modifiers and key hematopoietic transcription factors, such as KLF6, BCL6 and RUNX3. Notably, in vitro downregulation of KLF6 results in impaired differentiation, increased colony forming potential and changes in expression that recapitulate aging and leukemia signatures. Thus, age-associated epigenetic reprogramming may form a predisposing condition for the development of age-related AML. Overall design: We profiled the human HSCe (Lineage-, CD34+, CD38-) transcriptome with aging at the single cell level. Single-cell RNAseq was performed on FACS isolated human bone marrow derived HSCe from 5 young (24-37 yo) and 4 aged donor (64-71 yo). Donors had no known hematological malignancy.
Publication Title
Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 3000
Description
Aging is associated with functional decline of hematopoietic stem cells (HSC) as well as an increased risk of myeloid malignancies. We performed an integrative characterization of epigenomic and transcriptomic changes, including single-cell RNA-seq, during normal human aging. Lineage-CD34+CD38- cells (HSC-enriched, HSCe) undergo age-associated epigenetic reprogramming consisting of redistribution of DNA methylation and reductions in H3K27ac, H3K4me1 and H3K4me3. This reprogramming of aged HSCe globally targets developmental and cancer pathways which are comparably altered in AML of all ages; encompassing loss of 4,656 active enhancers, 3,091 bivalent promoters, and deregulation of several epigenetic modifiers and key hematopoietic transcription factors, such as KLF6, BCL6 and RUNX3. Notably, in vitro downregulation of KLF6 results in impaired differentiation, increased colony forming potential and changes in expression that recapitulate aging and leukemia signatures. Thus, age-associated epigenetic reprogramming may form a predisposing condition for the development of age-related AML. Overall design: CRISPR-Cas9 mediated knockout of KLF6 was performed in human peripheral blood CD34+ cells (n=4 replicates). RNA-seq was utilized to determine the effect of KLF6 knockout compared to a non-targeting control control.
Publication Title
Aging Human Hematopoietic Stem Cells Manifest Profound Epigenetic Reprogramming of Enhancers That May Predispose to Leukemia.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment, Subject
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Identification of genes differentially expressed in roots of Arabidopsis Col-0 and ndr1-1 mutants 48 h post inoculation with the fungal pathogen Verticillium longisporum.
Publication Title
Susceptibility to Verticillium longisporum is linked to monoterpene production by TPS23/27 in Arabidopsis.
Sample Metadata Fields
Age, Specimen part, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Gene expression profiling reveals a potential role of TCQA in neuronal and pigment cell differentiation of hAECs.
Publication Title
Regulating cell fate of human amnion epithelial cells using natural compounds: an example of enhanced neural and pigment differentiation by 3,4,5-tri-O-caffeoylquinic acid.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
The placenta is an understudied organ that has a critical role in mammalian development. In early placental development, the essential process of trophoblast invasion establishes adequate blood flow between mother and fetus. Despite its importance, little is known about the genomic regions responsible for regulating trophoblast invasion. In order to identify enhancers that are important for regulating the process, we carried out ChIP-Seq for an enhancer-associated mark at two time points during early placental development. Combining these data with RNA-Seq data and protein interaction data allowed us to construct a gene-enhancer network describing trophoblast invasion. Overall design: RNA-Seq at two time points in early placenta development (e7.5 an e9.5). There are 3 biological replicates per time point. Samples were pooled and sequenced on two lanes.
Publication Title
Changes in the enhancer landscape during early placental development uncover a trophoblast invasion gene-enhancer network.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
The identification of small molecules which either increase the number and/or enhance the activity of CD34+ hematopoietic stem and progenitor cells (HSPCs) during ex-vivo expansion has remained challenging. Applying an unbiased in vivo chemical screen in a transgenic (c-myb:EGFP) zebrafish embryo model, histone deacetylase inhibitors (HDACI) (valproic acid, resminostat and entinostat) were shown to significantly amplify the number of phenotypic hematopoietic precursors. The identified HDACIs were confirmed to significantly enhance also the expansion of human HSPCs during ex vivo treatment. Long-term functionality of ex vivo expanded human HSPCs was verified in a xenotransplantation model using NSG mice. However, the HDACI induced proliferation of HSPCs was associated with short-term functional changes. One of the identified hits, valproic acid (VPA), increased the adhesion capacity of CD34+ cells on primary mesenchymal stromal cells and reduced their chemokine-mediated migration capacity in vitro. In line with the reduced migratory potential in vitro, homing as well as early engraftment of VPA treated human CD34+ cells was significantly impaired in the xenotransplantation model. Our data confirms that HDACI treatment leads to a net expansion of HSPCs cells with long-term engraftment potential across different species. However impaired homing and short-term-engraftment has to be kept in mind when designing clinical transplantation protocols. In addition, our gene expression analysis (RNA-Seq) revealed expression of several genes that were altered in CD34+ cells by VPA treatment including cell adhesion molecules and Notch and wnt genes which has been shown to be involved in preservation of stem cell properties. Overall design: Gene expression analysis of in vitro expanded human HSPCs (CD34+ cells) by valproic acid
Publication Title
Zebrafish In-Vivo Screening for Compounds Amplifying Hematopoietic Stem and Progenitor Cells: - Preclinical Validation in Human CD34+ Stem and Progenitor Cells.
Sample Metadata Fields
Disease, Subject
View Samples