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Interaction with Cholangiocytes and Neutrophils

ABSTRACT: Interaction with Cholangiocytes and Neutrophils

PROVIDER: PRJNA612323 | ENA |

REPOSITORIES: ENA

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Interaction with Cholangiocytes and Neutrophils

Project description:Alcoholic hepatitis (AH) is a life-threatening disease with limited treatment options. The presence of cholestasis worsens prognosis but the responsible mechanism is unknown. AH results in infiltration of polymorphonuclear neutrophils (PMNs) in the liver, and cholestasis often reflects bile duct pathology, so we investigated whether and how PMNs interact with cholangiocytes in AH.

2020-03-13 | GSE146899 | GEO

Interaction of neutrophils and hepatic stellate cells promotes fibrosis in a mouse model of steatohepatitis

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MiRNA expression in embryonic murine hepatocytes versus murine cholangiocytes at E18.5

Project description:Differentially expressed miRNAs between hepatocytes (GFP-neg in SOX9-GFP mice) and cholangiocytes (GFP-pos in SOX9-GFP mice) in mice at E18.5. We want to compare miRNA population in biliary cells and parenchymal cells (depleted from hematopoietic cells) during liver development. Cholangiocytes specifically express the transcription factor Sox9. This enables to separate cholangiocytes from the rest of the liver parenchyma by FACS from Sox9-GFP transgenic mice. In conclusion, we want to compare miRNA population in our GFP+ cells (cholangiocytes) and our GFP- cells (liver parenchyma depleted from hematopoietic cells).

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Project description:Purpose: The aim of this study is to propose a computational model which can help in unravelling the mechanisms of initial bile duct lumen formation. Guided by the quantification of morphological features and expression of genes in developing bile ducts (cholangiocytes) from embryonic mouse liver, hypotheses for the mechanisms of biliary lumen formation were generated and tested with the model. Here, the RNA-sequencing data were collected from purified embryonic cholangiocytes at two developmental stages (E16 and E18).

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Project description:Despite the impact of bile duct disorders, treatment options remain very limited. Poor access to biliary tissue and restrictions in long-term culture or significant expansion of primary cholangiocytes have posed major challenges for research in the field. These limitations have so far precluded large scale experiments such as transcriptomic and genome-wide analyses which are urgently needed to better understand biliary physiology and pathophysiology. To address this issue, we have developed a novel system for the isolation and propagation of primary cholangiocytes from the extrahepatic bile ducts. The resulting Extrahepatic Cholangiocyte Organoids (ECOs) maintain their genetic stability, transcriptomic profile and function over long term culture and are compatible with regenerative medicine applications such as biliary reconstruction. We established a novel protocol for the isolation and propagation of primary cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs). The aim of this experiment was to provide in depth characterisation of the transcriptome of ECOs during long term culture. We compare the transcriptome of ECOs cultured for 1 passage (P1), 10 passages (P10) and 20 passages (P20) with freshly isolated primary cholangiocytes from the common bile duct. Embryonic Stem Cells (ES) cells are used as a negative control=

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