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Homo sapiens
18 Downloadable Samples
Illumina HiSeq 3000
Description
Aims: Cardiovascular disease, one of the most common causes of death in western populations, is characterized by changes in RNA splicing and expression. Circular RNAs (circRNA) originate from back-splicing events, which link a downstream 5’ splice site to an upstream 3’ splice site. Several back-splicing junctions (BSJ) have been described in heart biopsies from human, rat and mouse hearts.[1,2] Here, we use human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) to identify circRNA and host gene dynamics in cardiac development and disease. In parallel, we explore candidate interactions of selected homologs in mouse and rat via RIP-seq experiments.Methods and Results: Deep RNA sequencing of cardiomyocyte development and ß-adrenergic stimulation uncovered 4,518 circRNAs. The set of circular RNA host genes is enriched for chromatin modifiers and GTPase activity regulators. RNA-seq and qRT-PCR data showed that circular RNA expression is highly dynamic in the hiPSC-CM model with 320 circRNAs showing significant expression changes. Intri-guingly, 82 circRNAs are independently regulated to their host genes. We validated the same circRNA dynamics for circRNAs from ATXN10, CHD7, DNAJC6 and SLC8A1 in biopsy material from human dilated cardiomyopathy (DCM) and control patients. Finally, we could show that rodent homologs of circMYOD, circSLC8A1, circATXN7 and circPHF21A interact with either the ribosome or Argonaute2 protein complexes.Conclusion: CircRNAs are dynamically expressed in a hiPSC-CM model of cardiac development and stress response. Some circRNAs show similar, host-gene inde-pendent expression dynamics in patient samples and may interact with the ribo-some and RISC complex. In summary, the hiPSC-CM model uncovered a new sig-nature of potentially disease relevant circRNAs which may serve as novel therapeu-tic targets.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Race
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer II
Description
The data contains RNA sequencing data of embryonic stem cell derived cells.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 36 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Epithelial-mesenchymal transition (EMT) is a pivotal process in development and disease. In carcinogenesis, various signaling pathways are known to trigger EMT by inducing the expression of EMT transcription factors (EMT-TFs) like SNAIL1, ultimately promoting invasion, metastasis and chemoresistance. However, how EMT is executed downstream of EMT-TFs is incompletely understood. Here, using human colorectal cancer (CRC) and mammary cell line models of EMT, we demonstrate that SNAIL1 critically relies on bone morphogenetic protein (BMP) signaling for EMT execution. This activity requires the transcription factor SMAD4 common to BMP/TGFβ pathways, but is TGFβ signaling-independent. Further, we define a signature of BMP-dependent genes in the EMT-transcriptome which orchestrate EMT-induced invasiveness, and are found to be regulated in human CRC transcriptomes and during EMT in vivo. Collectively, our findings substantially augment the knowledge of mechanistic routes whereby EMT can be effectuated, which is relevant for the conceptual understanding and therapeutic targeting of EMT processes.
Publication Title
Canonical BMP Signaling Executes Epithelial-Mesenchymal Transition Downstream of SNAIL1.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Therapeutic efficacy of first-generation hypomethylating agents (HMAs) is limited in elderly acute myeloid leukemia (AML) patients. Therefore, combination strategies with targeted therapies are urgently needed. Here, we discover that priming with SGI-110 (guadecitabine), a next-generation HMA, sensitizes AML cells to ASTX660, a novel antagonist of cellular Inhibitor of Apoptosis Protein 1 and 2 (cIAP1/2) and X-linked IAP (XIAP). Importantly, SGI-110 and ASTX660 synergistically induced cell death in a panel of AML cell lines as well as in primary AML samples while largely sparing normal CD34+ human progenitor cells, underlining the translational relevance of this combination. Unbiased transcriptome analysis revealed that SGI-110 alone or in combination with ASTX660 upregulated the expression of key regulators of both extrinsic and intrinsic apoptosis signaling pathways such as TNFRSF10B (DR5), FAS and BAX. Individual knockdown of the death receptors TNFR1, DR5 and FAS significantly reduced SGI-110/ASTX660-mediated cell death, whereas blocking antibodies for TRAIL or FASLG failed to provide protection. Also, TNF-blocking antibody Enbrel had little protective effect on SGI110/ASTX660-induced cell death. Further, SGI-110 and ASTX660 acted in concert to promote cleavage of caspase-8 and BID, thereby providing a link between extrinsic and intrinsic apoptotic pathways. Consistently, sequential treatment with SGI-110 and ASTX660 triggered loss of mitochondrial membrane potential (MMP) and BAX activation, which contributes to cell death as BAX silencing significantly protected from SGI-110/ASTX660-mediated apoptosis. Together, these events culminated in activation of caspases-3/-7, nuclear fragmentation and cell death. In conclusion, SGI-110 and ASTX660 cooperatively induced apoptosis in AML cells by engaging extrinsic and intrinsic apoptosis pathways, highlighting the therapeutic potential of this combination for AML.
Publication Title
Next-generation hypomethylating agent SGI-110 primes acute myeloid leukemia cells to IAP antagonist by activating extrinsic and intrinsic apoptosis pathways.
Sample Metadata Fields
Cell line
View Samples
SRP059989- Homo sapiens
- 10 Downloadable Samples
- IlluminaHiSeq2000
Description
By means of 3' end sequencing we provide a genome-wide, high-resolution polyadenylation map of the human heart. By sequencing 5 control en 5 dilated cardiomyopathy (DCM) myocardial specimens we investigate the difference in alternative polyadenylation (APA) in healthy and diseased hearts.
Publication Title
Genome-Wide Polyadenylation Maps Reveal Dynamic mRNA 3'-End Formation in the Failing Human Heart.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Class IIa histone deacetylases (HDACs) are signal-responsive regulators of gene expression involved in vascular homeostasis. To investigate the differential role of class IIa HDACs for the regulation of angiogenesis, we used siRNA to specifically suppress the individual HDAC isoenzymes. Among the HDAC isoforms tested, silencing of HDAC5 exhibited a unique pro-angiogenic effect evidenced by increased endothelial cell migration, sprouting and tube formation. Consistently, overexpression of HDAC5 decreased sprout formation, indicating that HDAC5 is a negative regulator of angiogenesis. The anti-angiogenic activity of HDAC5 was independent of MEF2 binding and its deacetylase activity, but required a nuclear localization indicating that HDAC5 might affect the transcriptional regulation of gene expression. To identify putative HDAC5 targets, we performed microarray expression analysis. Silencing of HDAC5 increased the expression of fibroblast growth factor 2 (FGF2) and angiogenic guidance factors including Slit2. Antagonization of FGF2 or Slit2 reduced sprout induction in response to HDAC5 siRNA. ChIP assays demonstrate that HDAC5 binds to the promoter of FGF2 and Slit2. In summary, HDAC5 represses angiogenic genes, like FGF2 and Slit2, which causally contribute to capillary-like sprouting of endothelial cells. The de-repression of angiogenic genes by HDAC5 inactivation may provide a useful therapeutic target for induction of angiogenesis.
Publication Title
HDAC5 is a repressor of angiogenesis and determines the angiogenic gene expression pattern of endothelial cells.
Sample Metadata Fields
Specimen part
View Samples SRP101375- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2500
Description
Control and H3K9me3-depleted (KDM4D OE) adult cardiac myocytes
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Homo sapiens
- 154 Downloadable Samples
Description
Posttraumatic stress disorder (PTSD) has been linked to immunologic dysregulation. Gene expression profiling has emerged as a promising tool for understanding the pathophysiology of PTSD. However, to date, all but one gene expression study was based on whole blood or unsorted peripheral blood mononuclear cell (PBMC), a complex tissue consisting of several populations of cells. The objective of this study was to utilize RNA sequencing to simultaneously profile the gene-expression of four immune cell subpopulations in World Trade Center responders. Pathway analyses identified gene sets related to immune response and inflammation as being among the differentially expressed genes in PTSD, including mast cell activation and regulation in CD4T, interferon-beta production in CD8T, and neutrophil related gene sets in monocytes. These findings are suggestive that immune cell dysregulation involves gene expression in various cell populations.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 96 Downloadable Samples
- IlluminaHiSeq1000
Description
K562 single cell RNA-seq study
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples SRP183700- Homo sapiens
- 30 Downloadable Samples
- NextSeq 500
Description
We examined skin biopsies from a diverse cohort of 23 SSc patients (including lesional forearm and non-lesional back samples) by RNA-seq. Metagenomic filtering and annotation was performed using the Integrated Metagenomic Sequencing Analysis (IMSA). Associations between microbiome composition and gene expression were analyzed using single-sample gene set enrichment analysis (ssGSEA).
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples