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Multi-omics profiling of cholangiocytes reveals chromatin state dynamics during hepatic cystogenesis in polycystic liver disease (ATAC-Seq female)

ABSTRACT: Through genome-wide profiling of chromatin dynamics, we revealed a profound increase of global chromatin accessibility and a switch from H3K9me3 to H3K9ac on cis-regulatory DNA elements of cyst-associated genes during cystogenesis. In an integrated epigenomic and transcriptomic analysis, we identified a transcription factor network associated with dynamic shifts in chromatin states. Functionally, we showed that inhibition of H3K9ac acetyltransferase or H3K9me3 demethylase restored chromatin states and gene expression program to slow cyst growth in PLD mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE237566 | GEO | 2023/07/18

REPOSITORIES: GEO

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Multi-omics profiling of cholangiocytes reveals chromatin state dynamics during hepatic cystogenesis in polycystic liver disease (ChIP-Seq)

Project description:Through genome-wide profiling of chromatin dynamics, we revealed a profound increase of global chromatin accessibility and a switch from H3K9me3 to H3K9ac on cis-regulatory DNA elements of cyst-associated genes during cystogenesis. In an integrated epigenomic and transcriptomic analysis, we identified a transcription factor network associated with dynamic shifts in chromatin states. Functionally, we showed that inhibition of H3K9ac acetyltransferase or H3K9me3 demethylase restored chromatin states and gene expression program to slow cyst growth in PLD mice.

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Multi-omics profiling of cholangiocytes reveals chromatin state dynamics during hepatic cystogenesis in polycystic liver disease (ATAC-Seq)

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Quantitative Proteomic Study Unmasks Fibrinogen Pathway in Polycystic Liver Disease

Project description:(1) Background: Polycystic liver disease (PLD) is a heterogeneous group of congenital disorders characterized by bile duct dilatation and cyst development derived from cholangiocytes. Nevertheless, the cystogenesis mechanism is currently unknown and the PLD treatment is limited to liver transplantation. Novel and efficient therapeutic approaches are th6us needed. In this context, the present work has a principal aim to find novel molecular pathways, as well as new therapeutic targets, involved in the hepatic cystogenesis process. (2) Methods: Quantitative proteomics based on SWATH–MS technology were performed comparing hepatic proteomes of Wild Type and mutant/polycystic livers in a polycystic kidney disease (PKD) murine model (Pkd1cond/cond;Tam-Cre−/+). (3) Results: We identified several proteins altered in abundance, with twofold cut-off up-regulation or down-regulation and an adjusted p-value significantly related to hepatic cystogenesis. Then, we performed enrichment and a protein–protein analysis identifying a cluster focused on hepatic fibrinogens. Finally, we validated a selection of targets by RT-qPCR, Western blotting and immunohistochemistry, finding a high correlation with quantitative proteomics data and validating the fibrinogen complex. (4) Conclusions: This work identified a novel molecular pathway in cystic liver disease, highlighting the fibrinogen complex as a possible new therapeutic target for PLD.

2022-04-04 | PXD031253 | Pride

Illumina Human Polycystic Liver Disease and Normal Biliary Stem Cell RNAseq

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2020-09-29 | PXD021139 | Pride

Targeting UBC9-mediated Protein Hyper-SUMOylation in Cystic Cholangiocytes Halts Polycystic Liver Disease in Experimental Models

2020-09-29 | PXD021140 | Pride