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

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

PROVIDER: PRJNA1019384 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26132830_1.fastq.gz	Fastqsanger.gz
	SRR26132830_2.fastq.gz	Fastqsanger.gz
	SRR26132831_1.fastq.gz	Fastqsanger.gz
	SRR26132831_2.fastq.gz	Fastqsanger.gz

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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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Project description:Hepatocellular carcinoma (HCC) formation is a multi-step pathological process that involves evolution of a heterogeneous immunosuppressive tumor microenvironment. However, the specific cell populations involved and their origins and contribution to HCC development remain largely unknown. Here, comprehensive single-cell transcriptome sequencing was applied to profile rat models of toxin-induced liver tumorigenesis and HCC patients. Specifically, we identified three populations of hepatic parenchymal cells emerging during HCC progression, termed metabolic hepatocytes (HCMeta), Epcam+ population with differentiation potential (EP+Diff) and immunosuppressive malignant transformation subset (MTImmu). These distinct subpopulations form an oncogenic trajectory depicting a dynamic landscape of hepatocarcinogenesis, with signature genes reflecting the transition from EP+Diff to MTImmu. Importantly, GPNMB+Gal-3+ MTImmu cells exhibit both malignant and immunosuppressive properties. Moreover, SOX18 is required for the generation and malignant transformation of GPNMB+Gal-3+ MTImmu cells. Enrichment of the GPNMB+Gal-3+ MTImmu subset was found to be associated with poor prognosis and a higher rate of recurrence in patients. Collectively, we unraveled the single-cell HCC progression atlas and uncovered GPNMB+Gal-3+ parenchymal cells as a major subset contributing to the immunosuppressive microenvironment thus malignance in HCC.

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