PMID- 37784089
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231122
IS  - 2045-3701 (Print)
IS  - 2045-3701 (Electronic)
IS  - 2045-3701 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Oct 2
TI  - CD24(+)LCN2(+) liver progenitor cells in ductular reaction contributed to 
      macrophage inflammatory responses in chronic liver injury.
PG  - 184
LID - 10.1186/s13578-023-01123-2 [doi]
LID - 184
AB  - BACKGROUND: CD24(+)CK19(+)/CD24(+)SOX9(+) resident liver cells are activated and 
      expanded after chronic liver injury in a ductular reaction. However, the sources 
      and functions of these cells in liver damage remain disputed. RESULTS: The 
      current study combined genetic lineage tracing with in vitro small-molecule-based 
      reprogramming to define liver progenitor cells (LPCs) derived from hepatic 
      parenchymal and non-parenchymal tissues. tdTom(+) hepatocytes were isolated from 
      ROSA26(tdTomato) mice following AAV8-Tbg-Cre-mediated recombination, EpCAM(+) 
      biliary epithelial cells (BECs) from wild-type intrahepatic bile ducts and 
      ALB/GFP(-)EpCAM(-) cells were isolated from Alb(CreERT)/R26(GFP) mice. A cocktail 
      of small molecules was used to convert the isolated cells into LPCs. These in 
      vitro cultured LPCs with CD24 and SOX9 expression regained the ability to 
      proliferate. Transcriptional profiling showed that the in-vitro cultured LPCs 
      derived from the resident LPCs in non-parenchymal tissues expressed Lipocalin-2 
      (Lcn2) at high levels. Accordingly, endogenous Cd24a(+)Lcn2(+) LPCs were 
      identified by integration of sc-RNA-sequencing and pathological datasets of liver 
      dysfunction which indicates that LPCs produced by ductular reactions might also 
      originate from the resident LPCs. Transplantation of in-vitro cultured 
      Cd24a(+)Lcn2(+) LPCs into CCl(4)-induced fibrotic livers exacerbated liver damage 
      and dysfunction, possibly due to LCN2-dependent macrophage inflammatory response. 
      CONCLUSIONS: CD24(+)LCN2(+) LPCs constituted the expanding ductular reaction and 
      contributed to macrophage-mediated inflammation in chronic liver damage. The 
      current findings highlight the roles of LPCs from distinct origins and expose the 
      possibility of targeting LPCs in the treatment of chronic hepatic diseases.
CI  - (c) 2023. Society of Chinese Bioscientists in America (SCBA).
FAU - Huang, Wei-Jian
AU  - Huang WJ
AD  - Department of Anesthesiology and Critical Care Medicine, School of Medicine, 
      Renji Hospital, Shanghai Jiaotong University, Shanghai, 200120, China.
AD  - Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of 
      Education, Shanghai, China.
AD  - Celliver Biotechnology Inc., Shanghai, China.
FAU - Qiu, Bi-Jun
AU  - Qiu BJ
AD  - Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao 
      Tong University., Shanghai, China.
FAU - Qi, Xiao-Shu
AU  - Qi XS
AD  - Department of Anesthesiology and Critical Care Medicine, School of Medicine, 
      Renji Hospital, Shanghai Jiaotong University, Shanghai, 200120, China.
AD  - Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of 
      Education, Shanghai, China.
FAU - Chen, Cai-Yang
AU  - Chen CY
AD  - Department of Anesthesiology and Critical Care Medicine, School of Medicine, 
      Renji Hospital, Shanghai Jiaotong University, Shanghai, 200120, China.
FAU - Liu, Wen-Ming
AU  - Liu WM
AD  - Department of Anesthesiology and Critical Care Medicine, School of Medicine, 
      Renji Hospital, Shanghai Jiaotong University, Shanghai, 200120, China.
AD  - Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of 
      Education, Shanghai, China.
AD  - Institute for Regenerative Medicine, Shanghai East Hospital, School of Life 
      Sciences and Technology, Tongji University, Shanghai, China.
FAU - Zhou, Shen-Ao
AU  - Zhou SA
AD  - Celliver Biotechnology Inc., Shanghai, China.
FAU - Ding, Min
AU  - Ding M
AD  - Department of Interventional Oncology, Renji Hospital, School of Medicine, 
      Jiaotong University, Shanghai, China.
FAU - Lu, Feng-Feng
AU  - Lu FF
AD  - Institute for Regenerative Medicine, Shanghai East Hospital, School of Life 
      Sciences and Technology, Tongji University, Shanghai, China.
FAU - Zhao, Jie
AU  - Zhao J
AD  - Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiao 
      Tong University., Shanghai, China.
FAU - Tang, Dan
AU  - Tang D
AD  - Department of Anesthesiology and Critical Care Medicine, School of Medicine, 
      Renji Hospital, Shanghai Jiaotong University, Shanghai, 200120, China.
AD  - Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of 
      Education, Shanghai, China.
FAU - Zhou, Xu
AU  - Zhou X
AD  - Department of Anesthesiology and Critical Care Medicine, School of Medicine, 
      Renji Hospital, Shanghai Jiaotong University, Shanghai, 200120, China.
AD  - Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of 
      Education, Shanghai, China.
FAU - Fu, Gong-Bo
AU  - Fu GB
AD  - Department of Medical Oncology, First School of Clinical Medicine, Jinling 
      Hospital, Southern Medical University, Nanjing, China.
FAU - Wang, Zhen-Yu
AU  - Wang ZY
AD  - State Key Laboratory of Oncogenes and Related Genes, School of Medicine, Renji 
      Hospital, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai, 
      China.
FAU - Ma, Hong-Qian
AU  - Ma HQ
AD  - Department of Anesthesiology and Critical Care Medicine, School of Medicine, 
      Renji Hospital, Shanghai Jiaotong University, Shanghai, 200120, China.
AD  - Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of 
      Education, Shanghai, China.
FAU - Wu, Yu-Ling
AU  - Wu YL
AD  - Department of Anesthesiology and Critical Care Medicine, School of Medicine, 
      Renji Hospital, Shanghai Jiaotong University, Shanghai, 200120, China.
AD  - Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of 
      Education, Shanghai, China.
FAU - Wu, Hong-Ping
AU  - Wu HP
AD  - International Cooperation Laboratory On Signal Transduction, Eastern 
      Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 
      China.
FAU - Chen, Xiao-Song
AU  - Chen XS
AD  - Department of Infectious Diseases, Renji Hospital, Shanghai Jiaotong University 
      School of Medicine, Shanghai, 200120, China. chenxiaosong@renji.com.
FAU - Yu, Wei-Feng
AU  - Yu WF
AD  - Department of Anesthesiology and Critical Care Medicine, School of Medicine, 
      Renji Hospital, Shanghai Jiaotong University, Shanghai, 200120, China. 
      ywf808@yeah.net.
AD  - Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of 
      Education, Shanghai, China. ywf808@yeah.net.
FAU - Yan, He-Xin
AU  - Yan HX
AUID- ORCID: 0000-0001-8390-650X
AD  - Department of Anesthesiology and Critical Care Medicine, School of Medicine, 
      Renji Hospital, Shanghai Jiaotong University, Shanghai, 200120, China. 
      hexinyw@163.com.
AD  - Key Laboratory of Anesthesiology (Shanghai Jiao Tong University), Ministry of 
      Education, Shanghai, China. hexinyw@163.com.
AD  - Celliver Biotechnology Inc., Shanghai, China. hexinyw@163.com.
AD  - Department of Interventional Oncology, Renji Hospital, School of Medicine, 
      Jiaotong University, Shanghai, China. hexinyw@163.com.
AD  - State Key Laboratory of Oncogenes and Related Genes, School of Medicine, Renji 
      Hospital, Shanghai Cancer Institute, Shanghai Jiaotong University, Shanghai, 
      China. hexinyw@163.com.
LA  - eng
GR  - 2018YFA0108200/National Key R&D Program/
GR  - 82270635/National Natural Science Foundation of China/
GR  - 82203378/National Natural Science Foundation of China/
GR  - 82100671/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20231002
PL  - England
TA  - Cell Biosci
JT  - Cell & bioscience
JID - 101561195
PMC - PMC10546777
OTO - NOTNLM
OT  - Ductular reaction
OT  - LCN2
OT  - Macrophages
OT  - Resident liver progenitor cells
OT  - Small molecule cocktail
COIS- The authors declare no competing interests.
EDAT- 2023/10/03 00:42
MHDA- 2023/10/03 00:43
PMCR- 2023/10/02
CRDT- 2023/10/02 23:47
PHST- 2023/04/10 00:00 [received]
PHST- 2023/08/30 00:00 [accepted]
PHST- 2023/10/03 00:43 [medline]
PHST- 2023/10/03 00:42 [pubmed]
PHST- 2023/10/02 23:47 [entrez]
PHST- 2023/10/02 00:00 [pmc-release]
AID - 10.1186/s13578-023-01123-2 [pii]
AID - 1123 [pii]
AID - 10.1186/s13578-023-01123-2 [doi]
PST - epublish
SO  - Cell Biosci. 2023 Oct 2;13(1):184. doi: 10.1186/s13578-023-01123-2.