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首都医科大学附属北京同仁医院首都医科大学附属同仁医院[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
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.
基金:
National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81773137, 31801227]; Guangzhou Health Care and Cooperative Innovation Major Project [201508020257, 201803040005]; Beijing Hospitals Authority Youth Programme [QML20180203]
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
共同第一作者:
通讯作者:
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
推荐引用方式(GB/T 7714):
Wang Haiyang,Feng Chao,Lu Meixin,et al.Integrative single-cell transcriptome analysis reveals a subpopulation of fibroblasts associated with favorable prognosis of liver cancer patients[J].TRANSLATIONAL ONCOLOGY.2021,14(1):doi:10.1016/j.tranon.2020.100981.
APA:
Wang, Haiyang,Feng, Chao,Lu, Meixin,Zhang, Biao,Xu, Yingchen...&Pei, Xuetao.(2021).Integrative single-cell transcriptome analysis reveals a subpopulation of fibroblasts associated with favorable prognosis of liver cancer patients.TRANSLATIONAL ONCOLOGY,14,(1)
MLA:
Wang, Haiyang,et al."Integrative single-cell transcriptome analysis reveals a subpopulation of fibroblasts associated with favorable prognosis of liver cancer patients".TRANSLATIONAL ONCOLOGY 14..1(2021)