{
  "abstract": "Background Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) effectively induces rapid liver hypertrophy in patients with initially unresectable liver tumours, yet the immunological mechanisms remain unclear.Objective We aim to elucidate the immune alterations and underlying mechanisms driving liver regeneration following ALPPS.Design The cohort study included single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics on remnant liver tissues from ALPPS patients. Neutrophil infiltration was validated by flow cytometry and histological analyses in the world’s largest ALPPS clinical cohort and mouse ALPPS models. Functional validation, including neutrophil depletion, matrix metalloproteinase 9 (MMP9) inhibition and CD177 blockade, as well as Cd177 knockout and CD177+ neutrophil infusion in vivo.Results scRNA-seq revealed substantial neutrophil infiltration following stage 1 ALPPS. Depletion of neutrophils impaired liver regeneration. Among subsets, CD177 + neutrophils were metabolically active with enhanced neutrophil extracellular traps formation and secreted MMP9. MMP9 inhibition disrupted extracellular matrix (ECM) degradation and hepatocyte growth factor alpha (HGF-α) release, impairing regeneration. CD177+ neutrophils interacted with endothelial cells via CD177–PECAM1 to facilitate transmigration, while hepatic stellate cell-derived CXCL8 promoted neutrophil chemotaxis via CXCL8–CXCR1/2. Cd177 deficiency attenuated neutrophil infiltration and regenerative growth, while CD177+ neutrophil infusion restored regeneration, which was abolished in Cd177−/− mice.Conclusions CD177 + neutrophils drive liver regeneration by promoting endothelial transmigration, ECM degradation and HGF-α release. These findings reveal a neutrophil-mediated mechanism driving surgical liver regeneration and support the potential of CD177+ neutrophil infusion to establish a proregenerative hepatic environment for therapeutic strategies in liver failure.",
  "authors": [
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China",
        "Zhongshan-BGI Precision Medical Center, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Jiayan Yan"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Ao Huang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China",
        "Zhongshan-BGI Precision Medical Center, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Shiyu Zhang"
    },
    {
      "affiliations": [
        "Laboratory of Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Na Yao"
    },
    {
      "affiliations": [
        "Liver Surgery Intensive Care Unit, Department of Intensive Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Junfeng Huang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China",
        "Zhongshan-BGI Precision Medical Center, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Zhifeng Jiang"
    },
    {
      "affiliations": [
        "Department of Nephrology, Shanghai Medical Center of Kidney and Shanghai Key Laboratory of Kidney and Blood Purification, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Jiayi Wang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Feiyu Chen"
    },
    {
      "affiliations": [
        "Zhongshan-BGI Precision Medical Center, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People’s Hospital, Shenzhen, China",
        "The Second Affiliated Hospital, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, China"
      ],
      "name": "Qichao Yu"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Jianwen Cheng"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Senquan Zhang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Tianyi Li"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Rongshan Gao"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Runze Miao"
    },
    {
      "affiliations": [
        "Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Rongkui Luo"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Shaolai Zhou"
    },
    {
      "affiliations": [
        "Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Yuan Ji"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Zheng Wang"
    },
    {
      "affiliations": [
        "Laboratory of Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China"
      ],
      "name": "Dongmei Gao"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Zhenbin Ding"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Zhaoyou Tang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Jia Fan"
    },
    {
      "affiliations": [
        "3DC STAR Laboratory, BGI CELL, Shenzhen, Guangdong, China",
        "Prince Fahad bin Sultan Research Chair for Biomedical Research, University of Tabuk, Tabuk, Saudi Arabia"
      ],
      "name": "Miguel A. Esteban"
    },
    {
      "affiliations": [
        "Department of Surgery, University of Regensburg Medical Center, Regensburg, Germany"
      ],
      "name": "Hans Jürgen Schlitt"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Xinrong Yang"
    },
    {
      "affiliations": [
        "Department of Hepatobiliary Surgery and Liver Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China",
        "Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China"
      ],
      "name": "Jian Zhou"
    }
  ],
  "title": "CD177+ neutrophils drive extracellular matrix remodelling and HGF-alpha release in ALPPS-induced liver regeneration",
  "uid": "63810ddb-4ba4-5198-b7b4-c09a83b79fcc"
}