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Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in Hepatocellular Carcinoma (Nanostring)

ABSTRACT: Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in Hepatocellular Carcinoma (Nanostring)

PROVIDER: PRJNA658540 | ENA |

REPOSITORIES: ENA

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Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in Hepatocellular Carcinoma (Nanostring)

Project description:Liver dysfunction is associated with diseases ranging from metabolic disorders to hepatocellular carcinomas (HCC). Here we employed single-cell RNA-sequencing to extensively characterise the cellular landscape of human liver, from development to disease. We analysed ~212,000 cells representing human fetal liver, HCC and mouse liver. Our analysis revealed a remarkable fetal-like reprogramming of the tumor microenvironment (TME). Specifically, the HCC ecosystem displayed features reminiscent of fetal development, including the re-emergence of fetal-associated endothelial cells (PLVAP+/VEGFR2+), and fetal-like (FOLR2+) tumor-associated macrophages (TAMs). In a cross-species comparative analysis, we discovered remarkable similarity of gene expression and regulatory networks between mouse embryonically-seeded, fetal-liver and FOLR2+ tumor macrophages. Spatial transcriptomics further corroborated a shared onco-fetal ecosystem between fetal-liver and HCC. Furthermore, gene regulatory analysis, spatial transcriptomics, and in vitro functional assays implicated VEGF and NOTCH signaling in maintaining onco-fetal ecosystem. Taken together, we report a shared immunosuppressive onco-fetal ecosystem between the human fetal-liver and HCC. Our results unravel a previously unexplored onco-fetal reprogramming of tumor ecosystem, provides a novel target for therapeutic interventions in HCC and also opens up avenues for identifying similar paradigms in other cancers and disease states.

2020-09-24 | GSE156626 | GEO

Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in Hepatocellular Carcinoma (scRNA-seq)

2020-09-24 | GSE156625 | GEO

Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in Hepatocellular Carcinoma

Project description:Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in Hepatocellular Carcinoma

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Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in Hepatocellular Carcinoma (scRNA-seq)

Project description:Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in Hepatocellular Carcinoma (scRNA-seq)

| PRJNA658541 | ENA

Clinical significance of apurinic/apyrimidinic endodeoxyribonuclease 1 and microRNAs axis in hepatocellular carcinoma [NanoString]

Project description:Hepatocellular carcinoma is the most frequent species of liver cancer and the identification of new prognostic factors opens new perspectives for therapy. Circulating and cellular onco-miRNAs are non coding RNAs which can control oncogenesis-related gene expression through post-transcriptional mechanisms and are considered novel prognostic and predictive factors in cancer biology. The apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) contributes in the quality control and processing of specific onco-miRNAs, and is a negative prognostic factor in many tumors. The present work aims: a) to define APE1 prognostic value in HCC; b) to identify miRNAs regulated by APE1 and their relative target genes, and c) to study their prognostic value.

2023-09-21 | GSE222851 | GEO

Onco-fetal reprogramming of endothelial cells drives immunosuppressive macrophages in Hepatocellular Carcinoma

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

2020-09-24 | GSE156337 | GEO

GPNMB+Gal-3+ Hepatic Parenchymal Cells Promote Immunosuppressive Microenvironment Formation and Hepatocellular Carcinogenesis.

Project description:Hepatocellular carcinoma (HCC) involves a multistep pathological process in which heterogenous cells are evolved to shape an immunosuppressive microenvironment. Yet it remains largely unknown regarding the specific cell populations and their evolving routes essential for HCC development. Here, we created a rat model mimicking human HCC and generated a single-cell resolution atlas to HCC development. Specifically, we identified three populations of hepatic parenchymal cells during HCC progression, i.e., metabolic hepatocyte (HC Meta ), hepatic progenitor cell-like population with differentiation potential (HPC-like Diff ) and immunosuppressive malignant transformation subset (H-M Immu ). These three distinct subpopulations formed an oncogenic trajectory depicting a dynamic landscape of hepatocyte carcinogenesis, with signature genes reflecting the transition from HPC-like Diff to H-M Immu . Cross-species comparative analysis further revealed the H-M Immu subset to be highly conserved. Importantly, the H-M Immu (GPNMB + Gal-3 + ) cells exhibit both malignant and immunosuppressive properties. Moreover, SOX18 was found to be required for the generation of GPNMB + Gal-3 + H-M Immu cells and for their ability to form tumors. Enrichment of GPNMB + Gal-3 + H-M Immu subset was found to be associated with poor prognosis and higher rate of recurrence for HCC patients. Collectively, we unraveled the single-cell evolving mechanism of HCC and uncovered GPNMB + Gal-3 + H-M Immu cells as a major subset contributing to the immunosuppressive microenvironment and HCC malignance

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GPNMB+Gal-3+ Hepatic Parenchymal Cells Promote Immunosuppressive Microenvironment Formation and Hepatocellular Carcinogenesis

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GPNMB+Gal-3+ Hepatic Parenchymal Cells Promote Immunosuppressive Microenvironment Formation and Hepatocellular Carcinogenesis.

Project description:GPNMB+Gal-3+ Hepatic Parenchymal Cells Promote Immunosuppressive Microenvironment Formation and Hepatocellular Carcinogenesis.

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Project description:GPNMB+Gal-3+ Hepatic Parenchymal Cells Promote Immunosuppressive Microenvironment Formation and Hepatocellular Carcinogenesis

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