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SRP114373
Mus musculus
7 Downloadable Samples
NextSeq 500
Description
The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury. Overall design: We generated transciptome data from proliferative cardiac cells collected from 3, 7 or 14 days following myocardial infarction (MI) or sham surgery. This series includes single-cell transcriptome data from (Ki67-RFP+) cardiac cells collected from neonatal murine hearts, adult homeostatic murine hearts or adult murine hearts collected 14 days following myocardial infarction (MI), ischemic/perfusion (I/R) or sham surgery.
Publication Title
Profiling proliferative cells and their progeny in damaged murine hearts.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 97 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The transcriptomics changes induced in the human liver cell line HepG2 by 17 hepatotoxic compounds, 5 non-hepatotoxic compounds and solvent controls after treatment for 24h
Publication Title
Classification of hepatotoxicants using HepG2 cells: A proof of principle study.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative cross-omics analysis in primary mouse hepatocytes unravels mechanisms of cyclosporin A-induced hepatotoxicity.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 23 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The transcriptomics changes induced in Primary Mouse Hepatocytes by Cyclosporin A after treatment for 24h and 48h
Publication Title
Integrative cross-omics analysis in primary mouse hepatocytes unravels mechanisms of cyclosporin A-induced hepatotoxicity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), (imblegenhumandnamethylation2.1mdeluxepromoterarray[100929hg19deluxeprommethhx1)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative "-Omics" Analysis in Primary Human Hepatocytes Unravels Persistent Mechanisms of Cyclosporine A-Induced Cholestasis.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), (imblegenhumandnamethylation2.1mdeluxepromoterarray[100929hg19deluxeprommethhx1)
Description
Cyclosporine A (CsA), is an endecapeptide with strong immunosuppressant activities and has contributed significantly towards clinical progress in organ transplantation. Furthermore, it has various toxic effects in the kidney and especially in the liver where it may induce cholestasis. The CsA drug-induced cholestasis (DIC) pathway includes important genes involved in the uptake, synthesis, conjugation and secretion of bile acids, which can be verified also in hepatic models in vitro. However, whether changes in CsA-induced cholestasis pathway induced in vitro are persistent thus presenting important biomarkers for repeated dose toxicity, has not yet been investigated. We therefore performed multiple -omics analyses, including whole genome analysis of DNA methylation, gene expression and microRNA expression in primary human hepatocytes (PHH) cultured in sandwich configuration, during and after terminating CsA treatment. For this, cells were exposed to a non-cytotoxic dose of 30 M CsA daily for 3 and 5 days. To investigate the persistence of induced changes upon terminating the CsA exposure of 5 days, a subset of PHH was subjected to a washout period (WO-period) of three days. DNA methylation (using NimbleGen 2.1 deluxe promoter arrays), transcriptomic (using Affymetrix Human Genome U133 Plus 2.0 arrays) and microRNA (using Agilent Sureprint G3 Unrestricted Human miRNA V16 8 60 K microarrays) analyses were performed on days 3, 5 and 8. Identification of differentially methylated genes (DMGs), differentially expressed genes (DEGs), and differentially expressed microRNAs (DE-miRs) was performed using several R packages. DMGs, DEGs and DE-miRs were found after CsA treatment of PHH for 3 and 5 days as well after the WO-period. Interestingly, 828 persistent DEGs and 6 persistent DE-miRs, but no persistent DMGs, were found after the WO-period. These persistent DEGs and DE-miRs showed concordance for 22 genes (13 genes upregulated in gene expression and downregulated in microRNA expression; 9 genes downregulated in gene expression and upregulated in microRNA expression). Some of the persistent transcriptomic changes as well as DE-miRs could be successfully mapped onto the DIC pathway, while epigenetic changes not. Furthermore, 29 persistent DEGs in vitro showed changes in the same direction as observed in livers from cholestasis patients. None of those 29 DEGs were present in the DIC pathway or cholestasis adverse outcome pathway. We have for the first time demonstrated a persistent impact of gene expression and microRNA expression related to DIC after repeated dose administration of CsA in vitro.
Publication Title
Integrative "-Omics" Analysis in Primary Human Hepatocytes Unravels Persistent Mechanisms of Cyclosporine A-Induced Cholestasis.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Homo sapiens
- 34 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The transcriptomics changes induced in the human liver cell line HepG2 by Cyclosporin A after treatment for 12h, 24h, 48h and 72h
Publication Title
Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Escherichia coli
- 12 Downloadable Samples
- Affymetrix E. coli Genome 2.0 Array (ecoli2)
Description
We measured transcriptional changes resulting from overexpression or downregulation of the GTPase Obg.
Publication Title
Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Orofacial clefts (OFCs) are the most frequent craniofacial birth defects. An orofacial cleft (OFC) occurs as a result of deviations in palatogenesis. Cell proliferation, differentiation, adhesion, migration and apoptosis are crucial in palatogenesis. We hypothesized that deregulation of these processes in oral keratinocytes contributes to OFC. We performed microarray expression analysis on palatal keratinocytes from OFC and non-OFC individuals. Principal component analysis showed a clear difference in gene expression with 24 and 17% for the first and second component respectively. In OFC cells, 228 genes were differentially expressed (p<0.001). Gene ontology analysis showed enrichment of genes involved in β1 integrin-mediated adhesion and migration, as well as in P-cadherin expression. A scratch assay demonstrated reduced migration of OFC keratinocytes (343.6 ± 29.62 μm) vs. non-OFC keratinocytes (503.4 ± 41.81 μm, p<0.05). Our results indicate that adhesion and migration are deregulated in OFC keratinocytes, which might contribute to OFC pathogenesis.
Publication Title
Deregulated Adhesion Program in Palatal Keratinocytes of Orofacial Cleft Patients.
Sample Metadata Fields
Specimen part
View Samples