Beta-catenin in cholangiocytes regulates immune environment and wound healing after hepatobiliary injury
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE155981 | GEO | 2021/10/14
REPOSITORIES: GEO
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Project description:Beta-catenin in cholangiocytes regulates immune environment and wound healing after hepatobiliary injury
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Project description:Human iPS cells were differentiated to cholangiocyte-like cells thorugh five phases of endodermal differentiation.
2016-08-25 | GSE86007 | GEO
Project description:Human iPS cells were differentiated to cholangiocyte-like cells thorugh five phases of endodermal differentiation. Human iPSC were generated by forced expression of the Yamanaka pluripotency factors. We then pursued a stepwise differentiation strategy toward iDCs, using precise temporal exposure to key biliary morphogens, and we characterized the cells, using a variety of morphologic, molecular, cell biologic, functional, and in vivo approaches.
2016-08-25 | E-GEOD-86007 | biostudies-arrayexpress
Project description:Cells of a human cholangiocyte cell line (H69) were exposed to 10 ng/ml of IFN-gamma for 8 h. Cells were collected and processed for miRNA array analysis carried out by EXIQON (Denmark).
2009-02-10 | E-MEXP-1906 | biostudies-arrayexpress
Project description:A β-catenin/T cell factor-dependent transcriptional program is critical during cutaneous wound repair for the regulation of scar size; however, the relative contribution of β-catenin activity and function in specific cell types in the granulation tissue during the healing process is unknown. Here, cell lineage tracing revealed that cells in which β-catenin is transcriptionally active express a gene profile that is characteristic of the myeloid lineage. Mice harboring a macrophage-specific deletion of the gene encoding β-catenin exhibited insufficient skin wound healing due to macrophage-specific defects in migration, adhesion to fibroblasts, and ability to produce TGF-β1. In irradiated mice, only macrophages expressing β-catenin were able to rescue wound-healing deficiency. Evaluation of scar tissue collected from patients with hypertrophic and normal scars revealed a correlation between the number of macrophages within the wound, β-catenin levels, and cellularity. Our data indicate that β-catenin regulates myeloid cell motility and adhesion and that β-catenin-mediated macrophage motility contributes to the number of mesenchymal cells and ultimate scar size following cutaneous injury.
| S-EPMC4089463 | biostudies-literature
Project description:Liver regeneration after injury is normally mediated by proliferation of hepatocytes, although recent studies have suggested biliary epithelial cells (BECs) can differentiate into hepatocytes during severe liver injury when hepatocyte proliferation is impaired. We investigated the effect of hepatocyte-specific β-catenin deletion in recovery from severe liver injury and BEC-to-hepatocyte differentiation. To induce liver injury, we administered choline-deficient, ethionine-supplemented (CDE) diet to three different mouse models, the first being mice with deletion of β-catenin in both BECs and hepatocytes (Albumin-Cre; Ctnnb1flox/flox mice). In our second model, we performed hepatocyte lineage tracing by injecting Ctnnb1flox/flox ; Rosa-stopflox/flox -EYFP mice with the adeno-associated virus serotype 8 encoding Cre recombinase under the control of the thyroid binding globulin promoter, a virus that infects only hepatocytes. Finally, we performed BEC lineage tracing via Krt19-CreERT ; Rosa-stopflox/flox -tdTomato mice. To observe BEC-to-hepatocyte differentiation, mice were allowed to recover on normal diet following CDE diet-induced liver injury. Livers were collected from all mice and analyzed by quantitative real-time polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence. We show that mice with lack of β-catenin in hepatocytes placed on the CDE diet develop severe liver injury with impaired hepatocyte proliferation, creating a stimulus for BECs to differentiate into hepatocytes. In particular, we use both hepatocyte and BEC lineage tracing to show that BECs differentiate into hepatocytes, which go on to repopulate the liver during long-term recovery. Conclusion: β-catenin is important for liver regeneration after CDE diet-induced liver injury, and BEC-derived hepatocytes can permanently incorporate into the liver parenchyma to mediate liver regeneration.
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Project description:Human in vivo skin wound: Non-wounded skin was obtained by taking punch biopsies from three healthy donors (donor 1,2 and 3). The samples were termed 'skin day 0 in vivo wound'. Skin wound samples were retrieved by making new punch biopsies from the edge of the original biopsies after four days. These samples were termed 'skin day 4 in vivo wound'. As much dermal tissue as possible was removed by dissection to make sure mainly epidermis was present in the samples. The samples were washed in NaCl to possible remove infiltrating inflammatory cells before RNA isolation. Ex vivo skin wounds: Skin was obtained from three healthy donors following reduction surgery (donor 1, 2, and 3). As much dermal tissue as possible was removed dissection. These samples were termed 'skin day 0 ex vivo wound'. Skin was sliced into 1x10 mm slices and incubated in keratinocyte medium for four days with either 1:1000 fold dilution of DMSO or 10 micromolar AG-1478 (dissolved in DMSO). Again as much dermal tissue was removed by dissection as possible before RNA was isolated. These samples were termed 'skin day 4 ex vivo wound' and 'skin day 4 AG-1478 ex vivo wound'. By comparing the gene expression day 4 in ex vivo wound with in vivo wounds it was possible to see which part of the gene expression in wounded skin that was due to the epidermal reaction to injury and how much was due to stimuli from infiltrating inflammatory cells absent in the ex vivo skin wounds. By comparing the data from ex vivo skin wounds day 4 with and without the EGFR-inhibitor AG-1478, it was possible to look at the importance of the EGF-receptor of EGFR for the gene expression in ex vivo wounded skin.
2011-09-13 | E-MEXP-3305 | biostudies-arrayexpress
Project description:The post-surgical fluid leakage from the tubular tissues is a critical symptom after gastrointestinal or urinary tract surgeries. Elucidating the mechanism for such abnormalities is vital in surgical and medical science. The exposure of the fluid such as peritonitis due to urinary or gastrointestinal perforation has been reported to induce severe inflammation to the surrounding tissue. However, there have been no reports for the tissue responses by fluid extravasation and assessment of post-surgical and injury complication processes is therefore vital. The current model mouse study aims to investigate the effect of the urinary extravasation of the urethral injuries. Analyses on the urinary extravasation affecting both urethral mesenchyme and epithelium and the resultant spongio-fibrosis/urethral stricture were performed. The urine was injected from the lumen of urethra exposing the surrounding mesenchyme after the injury. The wound healing responses with urinary extravasation were shown as severe edematous mesenchymal lesions with the narrow urethral lumen. The epithelial cell proliferation was significantly increased in the wide layers. The mesenchymal spongio-fibrosis was induced by urethral injury with subsequent extravasation. The current report thus offers a novel research tool for surgical sciences on the urinary tract.
| S-EPMC10313654 | biostudies-literature
Project description:Liver possesses robust regenerative ability, characterized by flexibility in the cellular source of regeneration based on the extent of the injury. After partial hepatectomy or minor injuries, hepatocytes, the primary liver cells, undergo self-duplication to replenish the liver mass. In contrast, when the damage is extensive, or hepatocyte proliferation is impaired, cholangiocytes contribute to hepatocyte recovery. This current paradigm of regenerative flexibility in the liver has been established for animals with little or no growth. However, the regenerative mechanisms during periods of growth in young animals remain unexplored. Here, we establish two new partial liver injury protocols in the zebrafish model of rapid growth during late larval stage and observe emergence of de novo hepatocytes in the presence of spared hepatocytes. Using single-cell RNA sequencing and lineage tracing, we identify cholangiocytes as the source of de novo hepatocytes. Our study offers a new perspective on the current paradigm of liver regenerating by proposing cholangiocyte-to-hepatocyte transdifferentiation as the default mechanism of hepatocyte recovery in late larval stage zebrafish.
2024-11-13 | GSE272484 | GEO
Project description:Microarray analysis comparing the expression profiles of siRNA-mediated CTNNB1-silenced and CTNNB1-retained HCC15 cells harboring a homozygous CTNNB1 S45F mutation revealed that besides several known Wnt genes, LGR6 was significantly downregulated by CTNNB1 knockdown in HCC15 cells.
2022-09-01 | GSE183178 | GEO