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GSE63232
Homo sapiens
2 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Drug-induced cardiac arrhythmia characterized by QT prolongation and torsade de pointes has been a major reason for drug withdrawal at the late stage of clinical trials. Current preclinical testing is still insufficient to identify drugs with pro-arrhythmic risks. Human induced pluripotent stem cell-derived cardiomyocytes are a promising development in safety screening as a reproducible human model. Using the patch-clamp technique, we showed that human induced pluripotent stem cell-derived cardiomyocytes exhibited spontaneous action potentials, which represent relatively immature forms of cardiac cells. Furthermore, in some spontaneously beating cells, a hERG blocker, E4031, depolarized membrane potentials and stopped spontaneous firing, resulting in failure to evaluate drug effects on electrophysiological parameters that reflect repolarization processes. Here we show that human stem cell-derived cardiomyocytes with transduced KCNJ2 encoding the inward-rectifier potassium channel have characteristics similar to mature cardiomyocytes including responsiveness to rate changes and potassium channel blockers. Our novel strategy could allow implementation of human induced pluripotent stem cell-derived cardiomyocytes in drug safety assessment for cardiac toxicity.
Publication Title
Overexpression of KCNJ2 in induced pluripotent stem cell-derived cardiomyocytes for the assessment of QT-prolonging drugs.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
Illumina HiSeq 2000
Description
Specialized tissue macrophages arise during embryogenesis from yolk-sac (YS) progenitors that migrate into developing tissues and terminally differentiate in situ. Until recently, it has been impossible to isolate or derive sufficient numbers of YS-derived macrophages for further study, but data now suggest that induced pluripotent stem cells (iPSCs) can be driven to undergo a process reminiscent of YS-hematopoiesis in vitro. We asked whether iPSC-derived primitive macrophages (iMac) can terminally differentiate into specialized macrophages using growth factors and organ-specific cues. Co-culturing murine iMac with iPSC-derived neurons promoted differentiation into microglia-like cells in vitro. Furthermore, murine iMac differentiated in vivo into microglia following injection into the brain, and functional alveolar macrophages after engraftment in the lung. Overall design: 24 samples, 12 iMac/iMicro, 12 BM-Mac/BM-Micro. Macrophages were analysed at 4 time points (day 0, 3, 6, 12), with 3 independent replicates for each time point. Non-cocultured samples from the same batch (Day 0 iMac/BM-Mac) were used as controls for the experiment.
Publication Title
Induced-Pluripotent-Stem-Cell-Derived Primitive Macrophages Provide a Platform for Modeling Tissue-Resident Macrophage Differentiation and Function.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Analysis of alternative splicing in heart (left ventricles) samples of 3 adult DM1 patients versus 3 adult controls Overall design: PolyA RNA from left ventricles (heart) of 3 controls and 3 DM1 patients were analysed by massive parrallel sequencing
Publication Title
Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Analysis of alternative splicing of left ventricles heart samples of 3 DM1 adult versus 3 adult controls
Publication Title
Splicing misregulation of SCN5A contributes to cardiac-conduction delay and heart arrhythmia in myotonic dystrophy.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Caenorhabditis elegans
- 20 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 20 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
Analysis of the transcriptional response to viral infection in C.elegans.
Publication Title
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The combination of Wnt pathway activation by the GSK3 inhibitor and ERK pathway inhibition by the MEK inhibitor, which is known as 2i is a well-established method to maintain mouse embryonic stem cell (mESC) self-renewal. Here we show that Activin A also has the ability to promote naive pluripotency of mESCs when combined with the MEK inhibitor PD0325901. mESCs were efficiently propagated in a medium containing both Activin A and the MEK inhibitor (PD0325901). mESCs cultured in Activin+PD retained a pluripotency state that expresses high levels of naive pluripotency-related transcription factors and is able to differentiate into three germ layers under appropriate conditions. They also showed naive pluripotency features, including the preferential usage of the Oct4 distal enhancer and the self-renewal response to Wnt pathway activation. Our finding provides another way to maintain the naive pluripotency state and reveals a role of Activin/Nodal/TGF- signaling in stabilizing self-renewal gene regulatory networks in mESCs.
Publication Title
Activin A in combination with ERK1/2 MAPK pathway inhibition sustains propagation of mouse embryonic stem cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Caenorhabditis elegans
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
Attempt to identify small non-coding RNAs that change in levels as a result of viral infection of C.elegans Overall design: Small non-coding RNA (18-30nt) was extracted from animals either infected with Orsay virus or uninfected as indicated.
Publication Title
Competition between virus-derived and endogenous small RNAs regulates gene expression in Caenorhabditis elegans.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The discreteness of cell fates is an inherent and fundamental feature of multicellular organisms. Here we show that cross-antagonistic mechanisms of actions of MyoD and PPARg, which are the master regulators of muscle and adipose differentiation, respectively, confer the robustness to the integrity of cell differentiation. Simultaneous expression of MyoD and PPARg in mesenchymal stem/stromal cells led to the generation of a mixture of multinucleated myotubes and lipid-filled adipocytes. Interestingly, hybrid cells, i.e., lipid-filled myotubes, were not generated, suggesting that these differentiation programs are mutually exclusive. Mechanistically, while exogenously expressed MyoD was rapidly degraded in adipocytes through ubiquitin-proteasome pathways, exogenously expressed PPARg was not down-regulated in myotubes. In PPARg-expressing myotubes, PPARg-dependent histone hyperacetylation was inhibited in a subset of adipogenic gene loci, including that of C/EBPa, an essential effector of PPARg. Thus, the cross-repressive interactions between MyoD- and PPARg-induced differentiation programs ensure the discrete cell fate decisions.
Publication Title
Antagonism between the master regulators of differentiation ensures the discreteness and robustness of cell fates.
Sample Metadata Fields
Cell line, Treatment
View Samples- Drosophila melanogaster
- 4 Downloadable Samples
- Illumina Genome Analyzer II
Description
The transition in developmental control from maternal to zygotic gene products marks a critical step in early embryogenesis. Here, we use GRO-seq analysis to map the genome-wide RNA polymerase distribution during the Drosophila maternal to zygotic transition. This analysis unambiguously identifies the zygotic transcriptome, and provides insight into its mechanisms of regulation. Overall design: Two replicates of GRO-seq at each time point.
Publication Title
Extensive polymerase pausing during Drosophila axis patterning enables high-level and pliable transcription.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples