Fate and Functional Roles of Prominin 1+ Cells in Liver Injury and Cancer [Quant-seq]
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE152718 | GEO | 2020/12/17
REPOSITORIES: GEO
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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
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
Project description:As many other tumors, a subset of gliobastoma is thought to be maintained by a restricted population of cancer cells, stem-like cells that express CD133 transmembrane protein. Expression levels of CD133 gene has been linked to a poor prognostic molecular subgroup and is not overexpressed by the PDGF-driven proneural group. Thus, the significance of CD133+ cells for gliomagenesis of the proneural group is undetermined. In addition, the role of the CD133 protein remains elusive and controversial, which results from the difficult isolation of CD133+ cells that has largely relied on the use of antibodies to ill-defined glycosylated epitopes of CD133. Here, we used a knockin lacZ reporter mouse, Prom1lacZ/+, to track Prom1+ cells in the brain and found that Prom1 (prominin1, murine CD133 homologue) is expressed by cells that co-express markers characteristic of neuronal, glial and vascular lineage phenotype. In proneural tumors derived from injection of RCAS-PDGF into the brain of tv-a;Ink4a-Arf-/- Prom1lacZ/+ mice, Prom1+ cells co-express markers for astrocytes and endothelial cells. Therefore, we characterize the tumor propagation in a murine model and found that the mice co-transplanted with Prom1 endothelium and proneural tumor spheres cells had significant tumor burden and vascular proliferation (angiogenesis). Specific genes in Prom1 endothelium are identified that code for endothelial signaling modulators that most likely support proneural tumor progression and can be potential targets for anti-angiogenic therapy. Cells were sorted via FACS to obtain a population of CD31+CD133- cells and a population of CD31+CD133+ cells. Total RNA was extracted from each population and gene expression was assayed on Affymetrix Mouse 430 2.0 arrays with one array per cell population.
2013-12-31 | E-GEOD-43931 | biostudies-arrayexpress
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
Project description:Fate and Functional Roles of Prominin 1+ Cells in Liver Injury and Cancer [Quant-seq]
| PRJNA640336 | ENA
Project description:As many other tumors, a subset of gliobastoma is thought to be maintained by a restricted population of cancer cells, stem-like cells that express CD133 transmembrane protein. Expression levels of CD133 gene has been linked to a poor prognostic molecular subgroup and is not overexpressed by the PDGF-driven proneural group. Thus, the significance of CD133+ cells for gliomagenesis of the proneural group is undetermined. In addition, the role of the CD133 protein remains elusive and controversial, which results from the difficult isolation of CD133+ cells that has largely relied on the use of antibodies to ill-defined glycosylated epitopes of CD133. Here, we used a knockin lacZ reporter mouse, Prom1lacZ/+, to track Prom1+ cells in the brain and found that Prom1 (prominin1, murine CD133 homologue) is expressed by cells that co-express markers characteristic of neuronal, glial and vascular lineage phenotype. In proneural tumors derived from injection of RCAS-PDGF into the brain of tv-a;Ink4a-Arf-/- Prom1lacZ/+ mice, Prom1+ cells co-express markers for astrocytes and endothelial cells. Therefore, we characterize the tumor propagation in a murine model and found that the mice co-transplanted with Prom1 endothelium and proneural tumor spheres cells had significant tumor burden and vascular proliferation (angiogenesis). Specific genes in Prom1 endothelium are identified that code for endothelial signaling modulators that most likely support proneural tumor progression and can be potential targets for anti-angiogenic therapy.
2013-12-31 | GSE43931 | GEO
Project description:To explore the functional difference between CD90+CD39+ and CD90+CD39- fibroblasts in human hypertrophic scar and normal skin, the gene expresson microarray was performed on Live CD49f- E-Cadherin- Lin- CD45- CD31- CD90+ CD39+ and Live CD49f- E-Cadherin- Lin- CD45- CD31- CD90+ CD39- cells sorted from suspension disgested from three human hypertrophic scar samples; and Live CD49f- E-Cadherin- Lin- CD45- CD31- CD90+ CD39+ cells sorted from suspension disgested from three human normal skin samples
2021-07-05 | GSE158766 | GEO
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
Project description:Objective: Alcoholic hepatitis (AH) is characterized by the expansion of ductular reaction (DR) cells and expression of liver progenitor cell (LPC) markers. The aim of this study was to identify the gene expression profile and associated genes of DR cells and to evaluate its weight in alcoholic disease progression. Design: KRT7+, KRT7- and total liver fractions were laser microdissected from liver biopsies (n=6) of patients with AH and whole transcriptome was sequenced. Gene signature was assessed in transcriptomic data from 41 patients with alcoholic liver disease. Pro-inflammatory profile was evaluated in tissue and serum samples and in human LPC organoids. Results: Transcriptome analysis of KRT7+ DR cells uncovered intrinsic gene pathways of DR and allowed identifying genes associated with DR expressed in AH. In addition, DR gene signature and associated genes correlated with disease progression and poor outcome in AH patients. Importantly, DR presented a pro-inflammatory profile with expression of CXC and CCL chemokines and was associated with infiltrating neutrophils. Moreover, LPC markers correlated with liver expression and circulating levels of inflammatory mediators. In vitro, human LPC organoids mimicked ductular reaction gene expression profile and produced chemokines. Moreover, LPC promoted neutrophil migration and enhanced their inflammatory profile. Conclusions: Here we report for the first time the gene expression signature of DR in AH and its association with disease progression. Functional and experimental analysis demonstrates that DR cells have a pro-inflammatory profile, and suggest their involvement in neutrophil recruitment and liver inflammatory response.
2019-01-11 | GSE100901 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-12-17 | GSE152748 | GEO