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Single-cell transcriptome reveals a novel mechanism of C-Kit+-liver sinusoidal endothelial cells in NASH.
Li, Hui-Yi; Gao, Yu-Xuan; Wu, Jun-Cheng; Li, Jing-Ze; Fu, Seng-Wang; Xu, Ming-Yi.
Afiliación
  • Li HY; Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, No. 551, Pudong-South Road, Shanghai, 200120, China.
  • Gao YX; Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, No. 551, Pudong-South Road, Shanghai, 200120, China.
  • Wu JC; Departments of Gastroenterology, The Third Affiliated Hospital of Soochow University, Changzhou, 213000, Jiangsu, China.
  • Li JZ; Endoscopy Center, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, 200120, China.
  • Fu SW; Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 100, Haining Rd, Shanghai, 200080, China. chenghong.fu@shgh.cn.
  • Xu MY; Department of Gastroenterology, Shanghai East Hospital, Tongji University School of Medicine, No. 551, Pudong-South Road, Shanghai, 200120, China. xumingyi@tongji.edu.cn.
Cell Biosci ; 14(1): 31, 2024 Mar 09.
Article en En | MEDLINE | ID: mdl-38461242
ABSTRACT

AIM:

To understand how liver sinusoidal endothelial cells (LSECs) respond to nonalcoholic steatohepatitis (NASH).

METHODS:

We profiled single-LSEC from livers of control and MCD-fed mice. The functions of C-Kit+-LSECs were determined using coculture and bone marrow transplantation (BMT) methods.

RESULTS:

Three special clusters of single-LSEC were differentiated. C-Kit+-LSECs of cluster 0, Msr1+-LSECs of cluster 1 and Bmp4+Selp+-VECs of cluster 2 were revealed, and these cells with diverse ectopic expressions of genes participated in regulation of endothelial, fibrosis and lipid metabolism in NASH. The number of C-Kit+-primary LSECs isolated from MCD mice was lower than control mice. Immunofluorescence co-staining of CD31 and C-KIT showed C-Kit+-LSECs located in hepatic sinusoid were also reduced in NASH patients and MCD mice, compared to AIH patients and control mice respectively. Interestingly, lipotoxic hepatocytes/HSCs cocultured with C-Kit+-LSECs or the livers of MCD mice receipting of C-Kit+-BMCs (bone marrow cells) showed less steatosis, inflammation and fibrosis, higher expression of prolipolytic FXR and PPAR-α, lower expression of TNF-α and α-SMA. Furthermore, coculturing or BMT of C-Kit+-endothelial derived cells could increase the levels of hepatic mitochondrial LC3B, decrease the degree of mitochondrial damage and ROS production through activating Pink1-mediated mitophagy pathway in NASH.

CONCLUSIONS:

Hence, a novel transcriptomic view of LSECs was revealed to have heterogeneity and complexity in NASH. Importantly, a cluster of C-Kit+-LSECs was confirmed to recovery Pink1-related mitophagy and NASH progression.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Biosci Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Biosci Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido