Single-Cell RNA Transcriptomics Reveals the State of Hepatic Lymphatic Endothelial Cells in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure
Acute-on-chronic liver failure (ACLF) is an acutely decompensated cirrhosis syndrome with high short-term mortality. Very little is known about the relationship between the lymphatic system and ACLF. We explored the role of hepatic lymphatic vessels (LVs) and lymphatic endothelial cells (LyECs) in A...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-05-01
|
| Series: | Journal of Clinical Medicine |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2077-0383/11/10/2910 |
| _version_ | 1797498851265871872 |
|---|---|
| author | Pengpeng Zhang Hao Li Chen Zhou Kai Liu Bo Peng Xingguo She Ke Cheng Hong Liu Yingzi Ming |
| author_facet | Pengpeng Zhang Hao Li Chen Zhou Kai Liu Bo Peng Xingguo She Ke Cheng Hong Liu Yingzi Ming |
| author_sort | Pengpeng Zhang |
| collection | DOAJ |
| description | Acute-on-chronic liver failure (ACLF) is an acutely decompensated cirrhosis syndrome with high short-term mortality. Very little is known about the relationship between the lymphatic system and ACLF. We explored the role of hepatic lymphatic vessels (LVs) and lymphatic endothelial cells (LyECs) in ACLF using human liver samples with the help of single-cell RNA-sequencing (scRNA-seq) technology. Here, ACLF exhibited more severe liver injury and inflammation than cirrhosis, as indicated by significant increases in plasma levels of alanine/aspartate aminotransferases and total bilirubin. Compared with cirrhosis cases, the number of intrahepatic LVs was decreased significantly in ACLF patients. ScRNA-seq revealed that many monocyte/macrophages infiltrated into the liver of ACLF cases. Meanwhile, scRNA-seq revealed a group of apoptotic and dysfunctional LyECs, which were the result of secreted phosphoprotein 1 (SPP1) released from infiltrating monocyte/macrophages. In vitro, SPP1 increased the proportion of dead LyECs significantly and impaired the ability of tube formation of LyECs in a dose- and time-dependent manner. In conclusion, ACLF is associated with less LV and LyEC dysfunction, at least in part mediated by SPP1 released from infiltrating monocyte/macrophages. Hepatic LVs and LyECs can be a novel therapeutic strategy for ACLF. |
| first_indexed | 2024-03-10T03:39:16Z |
| format | Article |
| id | doaj.art-118c44fc40ae43aaafeede35e9393611 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T03:39:16Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-118c44fc40ae43aaafeede35e93936112023-11-23T11:36:44ZengMDPI AGJournal of Clinical Medicine2077-03832022-05-011110291010.3390/jcm11102910Single-Cell RNA Transcriptomics Reveals the State of Hepatic Lymphatic Endothelial Cells in Hepatitis B Virus-Related Acute-on-Chronic Liver FailurePengpeng Zhang0Hao Li1Chen Zhou2Kai Liu3Bo Peng4Xingguo She5Ke Cheng6Hong Liu7Yingzi Ming8The Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha 410013, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha 410013, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha 410013, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha 410013, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha 410013, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha 410013, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha 410013, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha 410013, ChinaThe Transplantation Center of the Third Xiangya Hospital, Central South University, Changsha 410013, ChinaAcute-on-chronic liver failure (ACLF) is an acutely decompensated cirrhosis syndrome with high short-term mortality. Very little is known about the relationship between the lymphatic system and ACLF. We explored the role of hepatic lymphatic vessels (LVs) and lymphatic endothelial cells (LyECs) in ACLF using human liver samples with the help of single-cell RNA-sequencing (scRNA-seq) technology. Here, ACLF exhibited more severe liver injury and inflammation than cirrhosis, as indicated by significant increases in plasma levels of alanine/aspartate aminotransferases and total bilirubin. Compared with cirrhosis cases, the number of intrahepatic LVs was decreased significantly in ACLF patients. ScRNA-seq revealed that many monocyte/macrophages infiltrated into the liver of ACLF cases. Meanwhile, scRNA-seq revealed a group of apoptotic and dysfunctional LyECs, which were the result of secreted phosphoprotein 1 (SPP1) released from infiltrating monocyte/macrophages. In vitro, SPP1 increased the proportion of dead LyECs significantly and impaired the ability of tube formation of LyECs in a dose- and time-dependent manner. In conclusion, ACLF is associated with less LV and LyEC dysfunction, at least in part mediated by SPP1 released from infiltrating monocyte/macrophages. Hepatic LVs and LyECs can be a novel therapeutic strategy for ACLF.https://www.mdpi.com/2077-0383/11/10/2910cirrhosisacute-on-chronic liver failurelymphangiogenesislymphatic endothelial cellsScRNA-seqsecreted phosphoprotein 1 |
| spellingShingle | Pengpeng Zhang Hao Li Chen Zhou Kai Liu Bo Peng Xingguo She Ke Cheng Hong Liu Yingzi Ming Single-Cell RNA Transcriptomics Reveals the State of Hepatic Lymphatic Endothelial Cells in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure Journal of Clinical Medicine cirrhosis acute-on-chronic liver failure lymphangiogenesis lymphatic endothelial cells ScRNA-seq secreted phosphoprotein 1 |
| title | Single-Cell RNA Transcriptomics Reveals the State of Hepatic Lymphatic Endothelial Cells in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure |
| title_full | Single-Cell RNA Transcriptomics Reveals the State of Hepatic Lymphatic Endothelial Cells in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure |
| title_fullStr | Single-Cell RNA Transcriptomics Reveals the State of Hepatic Lymphatic Endothelial Cells in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure |
| title_full_unstemmed | Single-Cell RNA Transcriptomics Reveals the State of Hepatic Lymphatic Endothelial Cells in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure |
| title_short | Single-Cell RNA Transcriptomics Reveals the State of Hepatic Lymphatic Endothelial Cells in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure |
| title_sort | single cell rna transcriptomics reveals the state of hepatic lymphatic endothelial cells in hepatitis b virus related acute on chronic liver failure |
| topic | cirrhosis acute-on-chronic liver failure lymphangiogenesis lymphatic endothelial cells ScRNA-seq secreted phosphoprotein 1 |
| url | https://www.mdpi.com/2077-0383/11/10/2910 |
| work_keys_str_mv | AT pengpengzhang singlecellrnatranscriptomicsrevealsthestateofhepaticlymphaticendothelialcellsinhepatitisbvirusrelatedacuteonchronicliverfailure AT haoli singlecellrnatranscriptomicsrevealsthestateofhepaticlymphaticendothelialcellsinhepatitisbvirusrelatedacuteonchronicliverfailure AT chenzhou singlecellrnatranscriptomicsrevealsthestateofhepaticlymphaticendothelialcellsinhepatitisbvirusrelatedacuteonchronicliverfailure AT kailiu singlecellrnatranscriptomicsrevealsthestateofhepaticlymphaticendothelialcellsinhepatitisbvirusrelatedacuteonchronicliverfailure AT bopeng singlecellrnatranscriptomicsrevealsthestateofhepaticlymphaticendothelialcellsinhepatitisbvirusrelatedacuteonchronicliverfailure AT xingguoshe singlecellrnatranscriptomicsrevealsthestateofhepaticlymphaticendothelialcellsinhepatitisbvirusrelatedacuteonchronicliverfailure AT kecheng singlecellrnatranscriptomicsrevealsthestateofhepaticlymphaticendothelialcellsinhepatitisbvirusrelatedacuteonchronicliverfailure AT hongliu singlecellrnatranscriptomicsrevealsthestateofhepaticlymphaticendothelialcellsinhepatitisbvirusrelatedacuteonchronicliverfailure AT yingziming singlecellrnatranscriptomicsrevealsthestateofhepaticlymphaticendothelialcellsinhepatitisbvirusrelatedacuteonchronicliverfailure |