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Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

ABSTRACT: Portal mesenchymal cells represent a very small amount of cells. They are tightly bound to the bile duct and portal vascular structures, relying on basement membranes. In the present study, we set up a specific procedure to isolate portal mesenchymal cells, for scRNAseq analysis. We identified 16 distinct cell clusters, including fibroblasts (5 clusters), vascular smooth muscle cells (VSCMs, 5 clusters), endothelial cells (4 clusters), HSCs (1 cluster) and mesothelial cells (1 cluster).

ORGANISM(S): Mus musculus

PROVIDER: GSE163777 | GEO | 2021/03/31

REPOSITORIES: GEO

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Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

Project description:Based on the identification of a transcriptomic signature, including Slit2, characterizing portal mesenchymal stem cells (PMSC) and derived myofibroblast (MF), we examined the gene expression profile of in liver tissue derived from multiple human liver disorders, including primary sclerosing cholangitis (PSC) (n=12), non-alcoholic steatohepatitis (NASH) (n=7) and other liver diseases (i.e., primary biliary cholangitis, autoimmune hepatitis, alcoholic liver disease and haemochromatosis) (n=8) and compared them to healthy controls (tumor free tissue from livers with metastasis from colorectal cancer) (n=5). We found that SLIT2 was overexpressed in the liver of patients with NASH, PSC and other chronic liver diseases. We also examined the microarray data of the human liver tissue samples for the transcriptomic signatures and found that in the different types of liver diseases the gene signature of PMSCs/PMSC-MFs was increased compared to normal liver, and correlated with the expression of ACTA2, COL1A1 and vWF.

2020-10-21 | GSE159676 | GEO

Identification of a portal vessel-associated fetal liver hematopoietic stem cell niche

Project description:Whereas the cellular basis of the hematopoietic stem cell (HSC) niche in the bone marrow has been characterized, the nature of the fetal liver (FL) niche is not yet elucidated. We show that Nestin+NG2+ pericytes associate with portal vessels, forming a niche promoting HSC expansion. Nestin+NG2+ cells and HSCs scale during development with the fractal branching patterns of portal vessels, tributaries of the umbilical vein. After closure of the umbilical inlet at birth, portal vessels undergo a transition from Neuropilin-1+Ephrin-B2+ artery to EphB4+ vein phenotype, associated with a loss of peri-portal Nestin+NG2+ cells and emigration of HSCs away from portal vessels. These data support a model in which HSCs are titrated against a peri-portal vascular niche with a fractal-like organization enabled by placental circulation. Characterization of the transcriptome of fetal liver and adult bone marrow niche using RNA-seq

2015-12-03 | E-GEOD-72341 | biostudies-arrayexpress

Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

Project description:Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

| PRJNA687508 | ENA

Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

Project description:Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

| PRJNA670177 | ENA

Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

Project description:Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

| PRJNA688690 | ENA

Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

Project description:Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

| PRJNA688687 | ENA

Identification of a portal vessel-associated fetal liver hematopoietic stem cell niche

2015-12-03 | GSE72341 | GEO

Portal fibroblasts with mesenchymal stem cell features form a reservoir of proliferative myofibroblasts in liver fibrosis

Project description:We performed transcriptomic studies comparing phenotypically defined PMSCs (PDGFRa/CD34/CD9high:CD200low) to HSCs (Vitamin-A fluorescent) of high purity, using bulk RNAseq. We further extended bulk RNAseq analyses of the two cell populations to myofibroblasts derived from both cell types in culture, including an early and late stage of differentiation for PMSC-MFs. Comparative analyses of gene expression indicated that 100 genes in PMSCs and 112 genes in HSCs, i) were overexpressed according to both scRNAseq and bulk RNAseq analyses, and ii) remained differentially expressed in these cells throughout their myofibroblastic differentiation. We selected the most differentially expressed of these genes, to build a multigene expression signature of PMSCs/PMSC-MFs (7 genes) and of HSCs/HSC-MFs (6 genes).

2021-03-31 | GSE164037 | GEO

Portal Hypertension Induced Changes in Splenic Gene Expression

Project description:Splenomegaly is caused by several pathological conditions, including portal hypertension, which is most frequently caused by chronic liver disease (e.g., liver cirrhosis). The detailed mechanisms through which portal pressure induces splenomegaly and the precise pathophysiological conditions in portal hypertension-induced splenomegaly remain to be fully elucidated. We used microarrays to identify the differential gene expression underlying the portal hypertension-induced splenomegaly.

2018-11-21 | GSE113613 | GEO

Portal Hypertension Induced Changes in Splenic microRNA Expression

Project description:Splenomegaly is caused by several pathological conditions, including portal hypertension, which is most frequently caused by chronic liver disease (e.g., liver cirrhosis). The detailed mechanisms through which portal pressure induces splenomegaly and the precise pathophysiological conditions in portal hypertension-induced splenomegaly remain to be fully elucidated. We used microarrays to identify the differential microRNA expression underlying the portal hypertension-induced splenomegaly.

2018-11-21 | GSE113612 | GEO

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