Hepatic stellate cell single cell atlas reveals a highly similar activation process across liver disease aetiologies
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PROVIDER: PRJNA1159712 | ENA |
REPOSITORIES: ENA
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Project description:It is still unclear whether hepatic stellate cells (HSC) activate in a similar manner in different chronic liver disease aetiologies. Here, we investigate how human stellate cells activate in vitro at the transcriptome level.
2024-10-25 | GSE276915 | GEO
Project description:We generated a high-resolution cellular atlas of the healthy human liver by profiling the transcriptome of more than 25,000 individual liver cells using droplet-based RNA-sequencing. Recently published datasets and in situ hybridization were integrated to confirm, validate and locate newly identified cell populations. We identified, annotated and characterized a total of 23 cell subpopulations that represent the degree of heterogeneity of parenchymal (i.e. hepatocytes and cholangiocytes) and non-parenchymal liver cells (i.e. endothelial cells, stellate cells, macrophages and lymphoid cells). We successfully classified human hepatocytes and liver sinusoidal endothelial cells along the porto-central axis and for the first time reveal the existence of functionally specialized pericentral GPC3+ and periportal HHIP+ DBH+ hepatic stellate cells in the healthy human liver. Our study provides a description of the different cell compartments that enter into the composition of a healthy human liver and currently constitutes the biggest single-cell RNA sequencing dataset available on human healthy hepatocytes and hepatic stellate cells. We identified subsets of hepatic stellate cells characterized by distinct localization and physiological functions.
2021-04-26 | GSE158723 | GEO
Project description:Analysis of human hepatic stellate cell line LX2 stimulated for 24h in serum-free DMEM medium containing 0 or 50 ng/ml recombinant human GDF2 protein. Results provide insight into the activation effects of GDF2 on human hepatic stellate cell. We used microarrays to detail the global programme of gene expression underlying activation of hepatic stellate cells and identified liver-fibrosis-related genes genes during this process.
2019-09-05 | GSE104482 | GEO
Project description:Gene expression throughout the reproductive process in rice (Oryza sativa) beginning with primordia development through pollination/fertilization to zygote formation was analyzed. We analyzed 25 stages/organs of rice reproductive development including early microsporogenesis stages with 57,381 probe sets, and identified around 26,000 expressed probe sets in each stage. Fine dissection of 25 reproductive stages/organs combined with detailed microarray profiling revealed dramatic, coordinated and finely tuned changes in gene expression. Decrease of expressed genes in the pollen maturation process was observed in a similar way with Arabidopsis and maize. An almost equal number of ab initio predicted genes and cloned genes appeared or disappeared coordinated with developmental stage progression. A large number of organ-/stage-specific genes were identified; notably 2,593 probe sets for developing anther, including 932 probe sets corresponding to ab initio predicted genes. Analysis of cell cycle-related genes revealed that several CDKs, cyclins and components of SCF E3 ubiquitin ligase complexes were expressed specifically in reproductive organs. Cell wall biosynthesis or degradation protein genes and transcription factor genes expressed specifically in reproductive stages were also newly identified. Rice genes homologous to reproduction-related genes in other plants showed expression profiles both consistent and inconsistent with their predicted functions. The rice reproductive expression atlas is likely to be the deepest and most comprehensive dataset available, indispensable for unraveling functions of many specific genes in plant reproductive processes that have not yet been thoroughly analyzed. This SuperSeries is composed of the following subset Series: GSE13988: Rice expression atlas (1): Anther development GSE14298: Rice expression atlas (2): Pollination - Fertilization GSE14299: Rice expression atlas (3): Early embryogenesis GSE14300: Rice expression atlas (4): Vegetative tissues GSE14301: Rice expression atlas (5): Anther development (Agilent data) Refer to individual Series
2010-11-11 | E-GEOD-14304 | biostudies-arrayexpress
Project description:Contrasting chromatin accessibility between activated and quiescent hepatic stellate cells to identify key gene networks for the activation process.
2023-10-11 | E-MTAB-12908 | biostudies-arrayexpress
Project description:Contrasting transcript expression between activated and quiescent hepatic stellate cells to identify key gene networks for the activation process.
2023-10-11 | E-MTAB-12909 | biostudies-arrayexpress
Project description:The p53 protein is a cell-autonomous tumor suppressor that restricts malignant transformation by triggering cell cycle exit or apoptosis. p53 also promotes cellular senescence, a program that triggers a stable cell cycle arrest and can modify the tissue microenvironment through its effect on cell membrane and secretory proteins. Here we show that specific ablation of p53 in hepatic stellate cells, which undergo a process of proliferation and senescence in the fibrogenic response to liver damage, enhances liver cirrhosis, reduces survival and increases the malignant transformation of adjacent epithelial cells into hepatocellular carcinoma. This p53-dependent senescence program involves the release of secreted proteins which skew macrophages into a tumor-inhibiting M1-state that can eliminate senescent stellate cells. In contrast, p53-deficient stellate cells secrete factors that promote M2 polarization, which is pro-tumorigenic. Our study reveals that p53 can exert a non-cell-autonomous tumor suppressor response and suggests that this occurs, in part, by its ability to influence macrophage polarization. We used microarrays to detail the global programme of gene expression underlying p53-dependent senescent and identified distinct classes of up-regulated or down-regulated genes during this process. Proliferating and senescent stellate cell pellets were collected RNA extraction and hybridization on Affymetrix microarrays.
2013-04-05 | E-GEOD-39469 | biostudies-arrayexpress
Project description:Activated hepatic stellate cells (HSC) that transdifferentiate to myofibroblasts in the injured liver are responsible for scar formation that leads to fibrosis and eventually cirrhosis. To investigate the gene expression profile during different stages of this process, we performed serial analysis of gene expression (SAGE), representing a quantitative and qualitative description of all expressed genes. Stellate cells were isolated from human livers and cultured. SAGE was performed on RNA isolated from quiescent, activated and transdifferentiated HSC. Comparison of the three resulting transcriptomes showed that less than 5% of all genes changed significantly in expression. Established markers of liver fibrosis showed enhanced expression in accordance with the transdifferentiation process. In addition, induction was seen for several genes not yet recognized to be involved in liver fibrosis, such as insulin-like growth factor binding proteins (IGFBP) and antagonists of bone morphogenic proteins: follistatin and gremlin. The induction of these genes was validated in vivo in mice developing liver fibrosis. The expression of IGFBPs and gremlin was measurable in the livers of these mice while it was low or undetectable in control mice without liver fibrosis. Since gremlin modulates the activity of bone morphogenic growth factors, it may represent a novel pathway and a target for therapeutic intervention and together with IGFBPs as a specific marker of liver fibrosis. In conclusion, the comparison of the three transcriptomes of (activated) stellate cells reveals novel genes involved in fibrogenesis and provides an appreciation of the sequence and timing of the fibrotic process in liver. Keywords: cell type comparison Human hepatic stellate cells (HSC) were isolated from wedge sections of normal human liver unsuitable for transplantation or from tumor-free human liver after partial hepatectomy as previously reported. Briefly, after a combined digestion with collagenase/pronase, HSC were separated from other liver nonparenchymal cells by ultracentrifugation over gradients of Larcoll (Sigma). The percentage of HSC in these isolates was > 90% as assessed by transmission microscopy, autofluorescence of vitamin A and immunofluorescence of vimentin. Immediately after isolation RNA was extracted for the construction of the SAGE library of quiescent HSC. To obtain activated stellate cells, these cells were cultured for 15 days on plastic culture dishes in modified Dulbecco's medium supplemented with 0.6 U/ml insulin, 2.0 mmol/L glutamine, 0.1 mmol/L nonessential amino acids, 1.0 mmol/L sodium pyruvate, antibiotic antifungal solution (Gibco) and 20% fetal bovine serum. To obtain fully transdifferentiated hepatic stellate cells, or myofibroblasts, the cells were cultured until they had reached passage 6 to 7. Myofibroblast phenotype was confirmed by detection of vimentin and ?-smooth muscle actin using immunofluorescence with monoclonal antibodies from Dako and Sigma, respectively. Medium was refreshed twice a week and at the indicated period RNA was extracted using Trizol (Quiagen)
2006-07-01 | E-GEOD-5022 | biostudies-arrayexpress
Project description:Early during culture of primary mouse HSCs gene expression changes. These expression alterations can be affected by treating cells with histone deacetylase inhibitor, valproic acid Primary mouse Hepatic stellate cells were cultured for short periods of time (4-16-64h) in presence or absence of valproic acid. Gene expression analysis (mouse Gene 1.0 ST arrays according to manufacturerM-bM-^@M-^Ys manual 701880Rev4 (Affymetrix, Santa Clara, CA)), in vitro stellate cell activation and inhibition of the activation by valproic acid treatment.
2014-01-01 | E-GEOD-51882 | biostudies-arrayexpress
Project description:A healthy human liver cell atlas reveals hepatic stellate cell heterogeneity
| PRJNA666353 | ENA