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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
- 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- 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
- 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- Drosophila melanogaster
- 1 Downloadable Sample
Illumina HiSeq 2000
Description
Neuroendocrine (NE) cells use large dense core vesicles (LDCVs) to traffic, process, store and secrete neuropeptide hormones through the regulated secretory pathway. The DIMM basic helix-loop-helix transcription factor of Drosophila controls the level of regulated secretory activity in NE cells. To pursue its mechanisms, we have performed two independent genome-wide analyses of DIMM's activities: (i) in vivo chromatin immunoprecipitation (ChIP) to define genomic sites of DIMM occupancy and (ii) deep sequencing of purified DIMM neurons to characterize their transcriptional profile. By this combined approach, we showed that DIMM binds to conserved E-boxes in enhancers of 212 genes whose expression is enriched in DIMM-expressing NE cells. DIMM binds preferentially to certain E-boxes within first introns of specific gene isoforms. Statistical machine learning revealed that flanking regions of putative DIMM binding sites contribute to its DNA binding specificity. DIMM's transcriptional repertoire features at least 20 LDCV constituents. In addition, DIMM notably targets the pro-secretory transcription factor, CREB-A, but significantly, DIMM does not target any neuropeptide genes. DIMM therefore prescribes the scale of secretory activity in NE neurons, by a systematic control of the regulated secretory pathway at steps that are both proximal and distal.
Publication Title
Genome-wide features of neuroendocrine regulation in Drosophila by the basic helix-loop-helix transcription factor DIMMED.
Sample Metadata Fields
Sex, Specimen part
View Samples- Drosophila melanogaster
- 7 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
To amass candidate DIMM targets in addition to Phm (Park et al., 2008a), we used genome-wide microarray profiling by over-expressing DIMM throughout the embryonic nervous system. We compared profiles from experimental (elav>dimm) and control (elav-GAL4) embryos at 22-26 hr and 28-32 hr after egg laying (AEL). The design was intended to identify transcripts consistently up-regulated shortly after the induction of DIMM; in so doing, we could circumvent the lethality that ensues in late embryonic, and/ or by early larval stages, due to pan-neuronal DIMM expression.
Publication Title
Molecular organization of Drosophila neuroendocrine cells by Dimmed.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mice lacking the transcription factor Fezf1 exhibit defects in the structural and molecular organiztion of their olfactory system. To invetigate this at the level of gene expression, we isolated Fezf1 expressing cells by FACS from the MOE of Fezf1+/- or Fezf1-/- animals and compared their gene expression profiles.
Publication Title
Fezf1 and Fezf2 are required for olfactory development and sensory neuron identity.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The c-Myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define the role of c-Myb in human hematopoietic lineage commitment, we studied the effects of its silencing during the commitment of human CD34+ Hematopoietic stem/progenitor cells. In CD34+ cells c-Myb silencing determined a cell cycle arrest in G0/G1 phase which strongly decreased the clonogenic efficiency, togheter with a reduction of erythroid colonies coupled with an increase of the macrophage and megakaryocyte ones. Moreover, morphological and flow cytometry data supported the preferential macrophage and megakaryocyte differentiation of c-Myb-silenced CD34+ cells. Taken together our data indicate that c-Myb is essential for the commitment along the erythroid and granulocyte lineages but not for the macrophage and megakaryocyte differentiation. Gene expression profiling of c-Myb-silenced CD34+ cells identified some potential c-Myb targets which can account for these effects, to study by Chromatin Immunoprecipitation and Luciferase Reporter Assay.
Publication Title
c-myb supports erythropoiesis through the transactivation of KLF1 and LMO2 expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 3 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The c-Myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define the role of c-Myb during the terminal differentiation of hematopoietic precursors, we studied the effects of its silencing in human primary CD14-myeloblasts, which maintain a granulo-monocyte differentiation bipotentiality. c-Myb-silenced myeloblasts were blocked in the G1 phase of the cell cycle at 24 hours post-nucleofection and subsequently were forced towards macrophage differentiation, as demonstrated by immunophenotypic and morphological analysis. Indeed, c-Myb-silenced CD14- cells differentiate to macrophage even after the treatment with ATRA 10-6 M, demonstrating that the c-Myb knockdown strongly impairs the ability of myeloblasts to differentiate to granulocytes. Gene expression profiling of c-Myb-silenced CD14- cells identified some potential c-Myb targets that can account for these effects.
Publication Title
c-myb supports erythropoiesis through the transactivation of KLF1 and LMO2 expression.
Sample Metadata Fields
Specimen part, Time
View Samples