The role of bone marrow-derived cells in the origin of liver cancer revealed by single-cell sequencing  

作　　者：Lu Chen Xianfu Yi Piao Guo Hua Guo Ziye Chen Chunyu Hou Lisha Qi Yongrong Wang Chengwen Li Peng Liu Yucun Liu Yuanfu Xu Ning Zhang 

机构地区：[1]The concrete information of affiliations should be presented,for instance,Department of Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Key Laboratory of Cancer Prevention and Therapy,Tianjin's Clinical Research Center for Cancer,Tianjin 300070,China [2]School of Biomedical Engineering and Technology,Tianjin Medical University,Tianjin 300070,China [3]The Center for Translational Cancer Research,Peking University First Hospital,Beijing 100034,China [4]State Key Laboratory of Experimental Hematology,National Clinical Research Center for Blood Diseases,Institute of Hematology&Blood Diseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China [5]CAMS Key Laboratory for Prevention and Control of Hematological Disease Treatment Related Infection,Tianjin 300020,China [6]Cytogenetics Laboratory,Institute of Hematology and Blood Diseases Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Tianjin 300020,China

出　　处：《Cancer Biology & Medicine》2020年第1期142-153,共12页癌症生物学与医学（英文版）

基　　金：supported by the grants from the National Natural Science Foundation of China(Grant No.81902401,81972656,31671421,81970107,81600083);the National 135 Major Project of China(Grant No.2018ZX10723204,2018ZX10302205);the Natural Science Foundation of Tianjin(Grant No.19JCQNJC09000);the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2018PT32034);CAMS Innovation Fund for Medical Sciences(Grant No.2016-12M-1-003);supported by the China Scholarship Council(Grant No.201906940003)。

摘　　要：Objective:Epithelial cancers often originate from progenitor cells,while the origin of hepatocellular carcinoma(HCC)is still controversial.HCC,one of the deadliest cancers,is closely linked with liver injuries and chronic inflammation,which trigger massive infiltration of bone marrow-derived cells(BMDCs)during liver repair.Methods:To address the possible roles of BMDCs in HCC origination,we established a diethylnitrosamine(DEN)-induced HCC model in bone marrow transplanted mice.Immunohistochemistry and frozen tissue immunofluorescence were used to verify DENinduced HCC in the pathology of the disease.The cellular origin of DEN-induced HCC was further studied by single cell sequencing,single-cell nested PCR,and immunofluorescence-fluorescence in situ hybridization.Results:Studies by using single cell sequencing and biochemical analysis revealed that HCC cells in these mice were coming from donor mice BMDCs,and not from recipient mice.Furthermore,the copy numbers of mouse orthologs of several HCC-related genes previously reported in human HCC were also altered in our mouse model.DEN-induced HCCs exhibited a similar histological phenotype and genomic profile as human HCCs.Conclusions:These results suggested that BMDCs are an important origin of HCC,which provide important clues to HCC prevention,detection,and treatments.

关 键 词：Hepatocellular carcinoma bone marrow-derived cells(BMDCs) ORIGINATION genome sequencing copy number alteration 

分 类 号：R735.7[医药卫生—肿瘤]