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Fate and Functional Roles of Prominin 1+ Cells in Liver Injury and Cancer

ABSTRACT: Fate and Functional Roles of Prominin 1+ Cells in Liver Injury and Cancer

PROVIDER: PRJNA640317 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12044347.fastq.gz	Fastqsanger.gz
	SRR12044348.fastq.gz	Fastqsanger.gz
	SRR12044349.fastq.gz	Fastqsanger.gz
	SRR12044350.fastq.gz	Fastqsanger.gz
	SRR12039793_1.fastq.gz	Fastqsanger.gz

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Fate and Functional Roles of Prominin 1+ Cells in Liver Injury and Cancer [Quant-seq]

Project description:Fate and Functional Roles of Prominin 1+ Cells in Liver Injury and Cancer [Quant-seq]

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Fate and Functional Roles of Prominin 1+ Cells in Liver Injury and Cancer [scRNA-seq]

Project description:Fate and Functional Roles of Prominin 1+ Cells in Liver Injury and Cancer [scRNA-seq]

| PRJNA640163 | ENA

Fate and functional roles of Prominin 1<sup>+</sup> cells in liver injury and cancer.

Project description:Prominin 1 (PROM1) is one of a few clinically relevant progenitor markers in human alcoholic hepatitis (AH) and hepatocellular carcinoma (HCC), and mouse liver tumor initiating stem cell-like cells (TICs). However, the origin, fate and functions of PROM1+ cells in AH and HCC are unknown. Here we show by genetic lineage tracing that PROM1+ cells are derived in part from hepatocytes in AH and become tumor cells in mice with diethyl nitrosamine (DEN)-initiated, Western alcohol diet-promoted liver tumorigenesis. Our RNA sequencing analysis of mouse PROM1+ cells, reveals transcriptomic landscapes indicative of their identities as ductular reaction progenitors (DRPs) and TICs. Indeed, single-cell RNA sequencing reveals two subpopulations of Prom1+ Afp- DRPs and Prom1+ Afp+ TICs in the DEN-WAD model. Integrated bioinformatic analysis identifies Discodin Domain Receptor 1 (DDR1) as a uniquely upregulated and patient-relevant gene in PROM1+ cells in AH and HCC. Translational relevance of DDR1 is supported by its marked elevation in HCC which is inversely associated with patient survival. Further, knockdown of Ddr1 suppresses the growth of TICs and TIC-derived tumor growth in mice. These results suggest the importance of PROM1+ cells in the evolution of liver cancer and DDR1 as a potential driver of this process.

| S-EPMC7656457 | biostudies-literature

Fate and Functional Roles of Prominin 1+ Cells in Liver Injury and Cancer [Quant-seq]

Project description:Purpose: The goal of the experiment is to obtain RNAseq profiles of Prom1+ Ductular Reactive Progenitors (DRPs) from mouse model of severe alcoholic liver injury Method: mRNA-seq analysis was performed in FACS sorted Prom1+CD49f+CD45-, Prom1-CD49f+CD45-, Prom1+CD49f+CD45+ cells and presorted CD45- liver cells. Conclusion: We obtained liver specific Prom1+ genes from analysis.

2020-12-17 | GSE152718 | GEO

Prominin-1-expressing Hepatic Progenitor Cells Induce Fibrogenesis in Murine Cholestatic Liver Injury

Project description:Purpose: Cholestatic liver injury is associated with intrahepatic biliary fibrosis, which can progress to cirrhosis. Resident hepatic progenitor cells (HPCs) expressing Prominin-1 (Prom1/CD133) become activated and participate in the expansion of cholangiocytes known as the ductular reaction. Previously, we demonstrated that in biliary atresia, Prom1(+) HPCs are present within developing fibrosis and that null mutation of Prom1 significantly abrogates fibrogenesis. Here, we hypothesized that these activated Prom1-expressing HPCs promote fibrogenesis in cholestatic liver injury. Methods: Using Prom1CreERT2-nLacZ/+;Rosa26Lsl-GFP/+ mice, we traced the fate of Prom1-expressing HPCs in the growth of the neonatal and adult livers and in biliary fibrosis induced by bile duct ligation (BDL). Results: Prom1-expressing cell lineage labeling with Green Fluorescent Protein (GFP) on postnatal day 1 exhibited an expanded population as well as bipotent differentiation potential towards both hepatocytes and cholangiocytes at postnatal day 35. However, in the adult liver, they lost hepatocyte differentiation potential. Upon cholestatic liver injury, adult Prom1-expressing HPCs gave rise to both PROM1(+) and PROM1(-) cholangiocytes contributing to ductular reaction without hepatocyte or myofibroblast differentiation. RNA-sequencing analysis of GFP(+) Prom1-expressing HPC lineage revealed a persistent cholangiocyte phenotype and evidence of Transforming Growth Factor-b pathway activation. Conclusion: Our data indicate that Prom1-expressing HPCs promote biliary fibrosis by activation of myofibroblasts in cholestatic liver injury.

2020-06-30 | GSE144726 | GEO

Fate and Functional Roles of Prominin 1+ Cells in Liver Injury and Cancer

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-12-17 | GSE152748 | GEO

Fate and Functional Roles of Prominin 1+ Cells in Liver Injury and Cancer [scRNA-seq]

Project description:Purpose: The goal of the study is to understand gene expression profiles of Prom1+ cells at single cell level in mouse liver cancer. Method: DEN-WAD liver from Col1a1Cre;Rosa26mTmG was perfused with collagenase. GFP+UV- cells were FACSsorted. Single cell library was constructed with 10X single gene expression v3 with 10X chromium technology. Conclusion: We identified Prom1+Afp+, Prom1+Afp-, Prom1-Afp+ gene expression profiles. These gene expression profiles revealed the markers previously observed for liver tumor intiating cells and ductular cells. In addition, they revealed novel specific markers.

2020-12-17 | GSE152707 | GEO

Prominin-1 promotes restitution of the murine extrahepatic biliary luminal epithelium following cholestatic liver injury

Project description:Restitution of the extrahepatic biliary luminal epithelium in cholangiopathies is poorly understood. Prominin-1 (Prom1) is a key component of epithelial ciliary body of stem/progenitor cells. Given that intrahepatic Prom1-expressing progenitor cells undergo cholangiocyte differentiation, we hypothesized that Prom1 may promote restitution of the extrahepatic bile duct (EHBD) epithelium following injury. Utilizing various murine biliary injury models, we identified Prom1-expressing cells in the peribiliary glands (PBGs) of the EHBD. These Prom1-expressing cells are progenitor cells which give rise to cholangiocytes as part of the normal maintenance of the EHBD epithelium. Following injury, these cells proliferate significantly more rapidly to re-populate the biliary luminal epithelium. Null mutation of Prom1 leads to significantly more than ten-fold dilated PBGs following rhesus rotavirus-mediated biliary injury. Cultured organoids derived from Prom1 knockout mice are comprised of biliary progenitor cells with altered apical-basal cellular polarity, significantly fewer and shorter cilia, and decreased organoid proliferation dynamics consistent with impaired cell motility. We, therefore, conclude that Prom1 is involved in biliary epithelial restitution following biliary injury in part through its role in supporting cell polarity.

2022-12-05 | GSE220054 | GEO

Prominin-1-expressing Hepatic Progenitor Cells Induce Fibrogenesis in Murine Cholestatic Liver Injury

Project description:Prominin-1-expressing Hepatic Progenitor Cells Induce Fibrogenesis in Murine Cholestatic Liver Injury

| PRJNA604713 | ENA

Prominin-1 promotes restitution of the murine extrahepatic biliary luminal epithelium following cholestatic liver injury

Project description:Prominin-1 promotes restitution of the murine extrahepatic biliary luminal epithelium following cholestatic liver injury

| PRJNA908254 | ENA