The role of bone marrow-derived cells in the origin of liver cancer revealed by single-cell sequencing
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...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
China Anti-Cancer Association
2020-02-01
|
| Series: | Cancer Biology & Medicine |
| Subjects: | |
| Online Access: | http://www.cancerbiomed.org/index.php/cocr/article/view/1567 |
| _version_ | 1818520123062878208 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Lu Chen |
| collection | DOAJ |
| description | 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 DEN-induced 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. |
| first_indexed | 2024-12-11T01:33:09Z |
| format | Article |
| id | doaj.art-fc87a8df64514067aedcb8d711ba6032 |
| institution | Directory Open Access Journal |
| issn | 2095-3941 |
| language | English |
| last_indexed | 2024-12-11T01:33:09Z |
| publishDate | 2020-02-01 |
| publisher | China Anti-Cancer Association |
| record_format | Article |
| series | Cancer Biology & Medicine |
| spelling | doaj.art-fc87a8df64514067aedcb8d711ba60322022-12-22T01:25:18ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412020-02-0117114215310.20892/j.issn.2095-3941.2019.0369The role of bone marrow-derived cells in the origin of liver cancer revealed by single-cell sequencingLu Chen0Xianfu Yi1Piao Guo2Hua Guo3Ziye Chen4Chunyu Hou5Lisha Qi6Yongrong Wang7Chengwen Li8Peng Liu9Yucun Liu10Yuanfu Xu11Ning Zhang12The 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, ChinaSchool of Biomedical Engineering and Technology, Tianjin Medical University, Tianjin 300070, ChinaThe 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, ChinaThe 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, ChinaThe 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, ChinaThe Center for Translational Cancer Research, Peking University First Hospital, Beijing 100034, ChinaThe 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, ChinaState 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, ChinaCytogenetics Laboratory, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, ChinaState 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, ChinaThe Center for Translational Cancer Research, Peking University First Hospital, Beijing 100034, ChinaState 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, ChinaThe 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, ChinaObjective: 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 DEN-induced 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.http://www.cancerbiomed.org/index.php/cocr/article/view/1567hepatocellular carcinomabone marrow-derived cells (bmdcs)originationgenome sequencingcopy number alteration |
| spellingShingle | 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 The role of bone marrow-derived cells in the origin of liver cancer revealed by single-cell sequencing Cancer Biology & Medicine hepatocellular carcinoma bone marrow-derived cells (bmdcs) origination genome sequencing copy number alteration |
| title | The role of bone marrow-derived cells in the origin of liver cancer revealed by single-cell sequencing |
| title_full | The role of bone marrow-derived cells in the origin of liver cancer revealed by single-cell sequencing |
| title_fullStr | The role of bone marrow-derived cells in the origin of liver cancer revealed by single-cell sequencing |
| title_full_unstemmed | The role of bone marrow-derived cells in the origin of liver cancer revealed by single-cell sequencing |
| title_short | The role of bone marrow-derived cells in the origin of liver cancer revealed by single-cell sequencing |
| title_sort | role of bone marrow derived cells in the origin of liver cancer revealed by single cell sequencing |
| topic | hepatocellular carcinoma bone marrow-derived cells (bmdcs) origination genome sequencing copy number alteration |
| url | http://www.cancerbiomed.org/index.php/cocr/article/view/1567 |
| work_keys_str_mv | AT luchen theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT xianfuyi theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT piaoguo theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT huaguo theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT ziyechen theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT chunyuhou theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT lishaqi theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT yongrongwang theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT chengwenli theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT pengliu theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT yucunliu theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT yuanfuxu theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT ningzhang theroleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT luchen roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT xianfuyi roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT piaoguo roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT huaguo roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT ziyechen roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT chunyuhou roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT lishaqi roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT yongrongwang roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT chengwenli roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT pengliu roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT yucunliu roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT yuanfuxu roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing AT ningzhang roleofbonemarrowderivedcellsintheoriginoflivercancerrevealedbysinglecellsequencing |