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Integrative single-cell transcriptome analysis reveals a subpopulation of fibroblasts associated with favorable prognosis of liver cancer patients

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机构: [1]Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China [2]South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China [3]Institute of Military Cognition and Brain Sciences, Academy of Military Medical Sciences, Beijing 100850, China [4]Department of Hepatobiliary Surgery, Beijing Tongren Hospital, Beijing 100730, China [5]Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, Beijing 100850, China [6]Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China
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关键词: Liver cancer Single-cell transcriptome Cancer-distinct fibroblast SPARCL1

摘要:
Single-cell transcriptome analysis has provided detailed insights into the ecosystem of liver cancer. However, the changes of the cellular and molecular components of liver tumors in comparison with normal livers have not been described at single-cell level. Here, we performed an integrative single-cell analysis of both normal livers and liver cancers. Principal component analysis was firstly performed to delineate the cell lineages in liver tissues. Differential gene expression within major cell types were then analyzed between tumor and normal samples, thus resolved the cell type-specific molecular alterations in liver cancer development. Moreover, a comparison between liver cancer derived versus normal liver derived cell components revealed that two subpopulations of fibroblasts were exclusively expanded in liver cancer tissues. By further defining subpopulation-specific gene signatures, characterizing their spatial distribution in tumor tissues and investigating their clinical significance, we found that the SPARCL1 positive fibroblasts, representing a group of tumor vessel associated fibroblasts, were related to reduced vascular invasion and prolonged survival of liver cancer patients. Through establishing an in-vitro endothelial-to-mesenchymal transition model, we verified the conversion of the fetal liver sinusoidal endothelial cells into the fibroblast-like cells, demonstrating a possible endothelial cell origination of the SPARCL1 positive fibroblasts. Our study provides new insights into the cell atlas alteration, especially the expanded fibroblasts in liver cancers.

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出版当年[2020]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学
最新[2025]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学
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出版当年[2019]版:
Q2 ONCOLOGY
最新[2024]版:
Q2 ONCOLOGY

影响因子: 最新[2024版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [1]Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China [2]South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China
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通讯机构: [1]Stem Cell and Regenerative Medicine Lab, Institute of Health Service and Transfusion Medicine, Beijing 100850, China [2]South China Research Center for Stem Cell & Regenerative Medicine, SCIB, Guangzhou 510005, China
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