Filters
Technology
Platform
GSE68001
Homo sapiens
9 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
Liver fibrosis is characterized by the excessive formation and accumulation of matrix proteins as a result of wound healing in the liver. A main event during fibrogenesis is the activation of the liver resident quiescent hepatic stellate cell (qHSC). Recent studies suggest that reversion of the activated HSC (aHSC) phenotype into a quiescent-like phenotype could be a major cellular mechanism underlying fibrosis regression in the liver, thereby offering new therapeutic perspectives for the treatment of liver fibrosis. The goal of the present study is to identify experimental conditions that can revert the activated status of human HSCs and to map the molecular events associated with this phenotype reversion by gene expression profiling
Publication Title
In vitro reversion of activated primary human hepatic stellate cells.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 1113 Downloadable Samples
Illumina HiSeq 2000, Illumina HiSeq 2500
Description
We successfully sequenced and annotated more than 400 cells from child, adult control, type 1 diabetes and type 2 diabetes donors. We detect donor-type specific transcript variation. We also report that cells from child donors have less defined gene signature. Cells from type 2 diabetes donors resemble juvenile cells in gene expression. Overall design: Cells from three adult controls (56, 74, 92), one donor with type 1 diabetes (91), two donors with type 2 diabetes (75, 143), and two child donors (40, 72) were sequenced. Numbers in parathesis indicates number of cells sequenced.
Publication Title
Single-Cell Transcriptomics of the Human Endocrine Pancreas.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Adult-derived human liver stem/progenitor cells (ADHLSC) are obtained after primary culture of the liver parenchymal fraction. The cells are of fibroblastic morphology and exhibit a hepato-mesenchymal phenotype. Hepatic stellate cells (HSC) derived from the liver non-parenchymal fraction present a comparable morphology as ADHLSC. Because both ADHLSC and HSC are described as liver stem/progenitor cells, we strived to extensively compare both cell populations at different levels and to propose tools demonstrating their singularity.
Publication Title
Gene expression profiling and secretome analysis differentiate adult-derived human liver stem/progenitor cells and human hepatic stellate cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
β cell apoptosis and dedifferentiation are two hotly-debated mechanisms underlying β cell loss in type 2 diabetes (T2D); however, the molecular drivers underlying such events remain largely unclear. Here, by performing a side-by-side comparison of mice carrying β cell-specific deletion of endoplasmic reticulum (ER)-associated degradation (ERAD) and autophagy, we report that while autophagy appears necessary for β cell survival, the highly conserved Sel1L-Hrd1 ERAD protein complex is required for the maintenance of β cell maturation and identity. Notably, SEL1L expression is significantly reduced in human T2D islets compared to healthy human islets. At the single cell level, we demonstrate that Sel1L deficiency is not associated with β cell loss, but rather loss of β cell identity. Mechanistically, we find that Sel1L-Hrd1 ERAD controls β cell identity via TGFβ signaling, in part by mediating the degradation of TGF-β receptor 1 (TGFβRI). Inhibition of TGFβ signaling in Sel1L-deficient β cells augments the expression of β cell maturation markers and increases the total insulin content. Our data reveal profound but distinct pathogenic effects of two major proteolytic pathways in β cells, providing a new framework for therapies targeting distinct mechanisms of protein quality control.
Publication Title
Sel1L-Hrd1 ER-associated degradation maintains β cell identity via TGF-β signaling.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2500
Description
Mitochondrial biogenesis and metabolism recently emerged as critical modulators of stemness properties and differentiation programmes. The increase in mitochondrial biogenesis and metabolic shift toward increased oxidative phosphorylations (OXPHOS) appear as hallmarks of stem cell differentiation processes. While several mechanisms support the involvement of mitochondrial biogenesis and function in the regulation of stem cell differentiation, the mechanisms triggering mitochondrial biogenesis in the context of cell differentiation remain elusive. In this study, we performed transcriptomic and bioinformatic analyses in order to get deeper insights into the cross-regulation of mitochondrial biogenesis and hepatogenic differentiation of human bone marrow mesenchymal stem cells (BM-MSCs). We identified a transcriptional regulatory network involved in the co-regulation of stem cell differentiation and mitochondrial biogenesis. Overall design: Transcriptomics analyses performed at early time points of the hepatogenic differentiation of BM-MSC
Publication Title
MPV17 does not control cancer cell proliferation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- IlluminaHiSeq2000, IlluminaGenomeAnalyzerIIx
Description
Type 2 diabetes mellitus (T2DM) is a multi-factorial disease characterized by the inability of beta-cells in the endocrine pancreas to produce sufficient amounts of insulin to overcome insulin resistance in peripheral tissue. To investigate the function of miRNAs in T2DM, we sequenced the small RNAs of human islets cells from diabetic and non-diabetic organ donors and identified a cluster of miRNAs in an imprinted locus on human chromosome 14 to be dramatically down-regulated in T2DM islets. These miRNAs are highly and specifically expressed in human beta-cells. The down-regulation of this imprinted locus strongly correlates with increased methylation of its promoter in T2DM islets, providing evidence for an epigenetic modification that contributes to the pathogenesis of T2DM. Targets of the Chr 14q32 cluster of miRNAs were identified by high-throughput sequencing of cross-linked and immunoprecipitated RNA (HITS-CLIP) of Argonaute. We have also identified a unique class of sequences, termed chimeric reads, that represent an in vivo ligation of miRNAs and their targets while in complex with Argonaute, and which allow for the direct identification of miRNA:target relationships in vivo. Overall design: There are three experiments in this submission. All are in human islets or islet cell types. The first is a comparison of miRNA levels in sorted alpha versus beta cells. There is one replicate for this experiment. The second experiment is to measure the expression of miRNAs in whole islets as a function of glucose levels. There are three levels and one replicate for each condition. The third exeriment is a comparison of whole islets taken from human donors that were suspected/confirmed Type 2 diabetic or considered controls. There are 3 controls and 4 T2D samples.
Publication Title
Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
The molecular determinants of a healthy human liver cell phenotype remain largely uncharacterized. In addition, the gene expression changes associated with activation of primary human hepatic stellate cells, a key event during fibrogenesis, remain poorly characterized. Here, we provide the transriptomic profile underpinning the healthy phenotype of human hepatocytes, liver sinusoidal endothelial cells (LSECs) and quiescent hepatic stellate cells (qHSCs) as well as activated HSCs (aHSCs)
Publication Title
Genome-wide analysis of DNA methylation and gene expression patterns in purified, uncultured human liver cells and activated hepatic stellate cells.
Sample Metadata Fields
Sex, Age, Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2000
Description
Type 2 diabetes mellitus (T2DM) is a complex disease characterized by the inability of the insulin-producing ß-cells in the endocrine pancreas to overcome insulin resistance in peripheral tissues. To determine if microRNAs are involved in the pathogenesis of human T2DM, we sequenced the small RNAs of human islets from diabetic and non-diabetic organ donors. We identified a cluster of miRNAs in an imprinted locus on human chromosome 14q32 that is highly and specifically expressed in human ß-cells and dramatically down-regulated in islets from T2DM organ donors. The down-regulation of this locus strongly correlates with hyper-methylation of its promoter. Using HITS-CLIP for the essential RISC-component Argonaute, we identified disease-relevant targets of the chromosome 14q32 microRNAs, such as IAPP and TP53INP1 that cause increased ß-cell apoptosis upon over-expression in human islets. Our results support a role for microRNAs and their epigenetic control by DNA methylation in the pathogenesis of T2DM. Overall design: Identification of miRNA-target interaction in human islets using HITS-CLIP, one mRNA library and one miRNA library
Publication Title
Epigenetic regulation of the DLK1-MEG3 microRNA cluster in human type 2 diabetic islets.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Unveiling the regulatory pathways maintaining hepatic stellate cells (HSC) in a quiescent (q) phenotype is essential to develop new therapeutic strategies to treat fibrogenic diseases. To uncover the miRNA-mRNAs regulatory interactions in qHSCs, HSCs were FACS-sorted from healthy livers and activated HSCs were generated in vitro. MiRNA Taqman array analysis showed HSCs expressed a low number of miRNA, from which 46 were down-regulated and 212 up-regulated upon activation. Computational integration of miRNA and gene expression profiles revealed that 66% of qHSCs miRNAs correlated with more than 6 altered targeted mRNAs (17,2810,7 targets/miRNA), whereas aHSC-associated miRNAs had an average of 1,49 targeted genes. Interestingly, interaction networks generated by miRNA-targeted genes in qHSCs were associated with key HSCs activation processes. Next, selected miRNAs were validated in healthy and cirrhotic human livers and miR-192 was chosen for functional analysis. Down-regulation of miR-192 in HSC was found to be an early event during fibrosis progression in mouse models of liver injury. Moreover, mimic assays for miR-192 in HSCs revealed its role in HSC activation, proliferation and migration. Together, these results uncover the importance of miRNAs in the maintenance of qHSC phenotype and form the basis for understanding the regulatory networks in HSCs.
Publication Title
Integrative miRNA and Gene Expression Profiling Analysis of Human Quiescent Hepatic Stellate Cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Hepatic stellate cells (HSC) are the main stromal cell component of the liver. In healthy liver, quiescent HSC participate in the homeostasis of extracellular matrix (ECM) and store vitamin A. Liver injury causes HSC activation, where they participate in the wound-healing response, by producing ECM components as well as cytokines involved in liver regeneration and inflammation. Moreover, HSC are the main cell type responsible for fibrosis progression. The lack of homogeneous cultures and renewable sources of human HSC has limited the studies of the role of HSC in liver injury, repair anf fibrosis. Here we report a procedure to direct the differentiation of human pluripotent stem cells (PSC) to HSC. The HSClike population (iPS-HSC) was enriched in PDGFR positive cells that expressed key HSC markers. Whole genome transcriptomic analysis revealed that iPS-HSC displayed features intermediate to quiescent and activated HSC. Functional analysis demonstrated that iPS-HSC accumulated retinyl esters into lipid droplets and responded to injury mediators. Moreover, when cultured with HepaRG hepatocytes as aggregates, iPS-HSC support long-term hepatocyte metabolic function and respond to hepatocyte toxicity by activating and promoting organoid fibrogenesis.
Publication Title
Generation of Hepatic Stellate Cells from Human Pluripotent Stem Cells Enables In Vitro Modeling of Liver Fibrosis.
Sample Metadata Fields
Specimen part
View Samples