Comparison of the single-cell and single-nucleus hepatic myeloid landscape within decompensated cirrhosis patients.

Autor:	Van Melkebeke L; Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium., Verbeek J; Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium., Bihary D; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.; VIB Center for Cancer Biology, Leuven, Belgium., Boesch M; Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium., Boeckx B; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.; VIB Center for Cancer Biology, Leuven, Belgium., Feio-Azevedo R; Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium., Smets L; Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium., Wallays M; Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium., Claus E; Department of Interventional Radiology, University Hospitals Leuven, Leuven, Belgium., Bonne L; Department of Interventional Radiology, University Hospitals Leuven, Leuven, Belgium., Maleux G; Department of Interventional Radiology, University Hospitals Leuven, Leuven, Belgium., Govaere O; Department of Imaging and Pathology, Translational Cell and Tissue Research, KU Leuven and University Hospitals Leuven, Leuven, Belgium., Korf H; Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium., Lambrechts D; Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven, Leuven, Belgium.; VIB Center for Cancer Biology, Leuven, Belgium., van der Merwe S; Laboratory of Hepatology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium.; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2024 Feb 06; Vol. 15, pp. 1346520. Date of Electronic Publication: 2024 Feb 06 (Print Publication: 2024).
DOI:	10.3389/fimmu.2024.1346520
Abstrakt:	Background and Aims: A complete understanding of disease pathophysiology in advanced liver disease is hampered by the challenges posed by clinical specimen collection. Notably, in these patients, a transjugular liver biopsy (TJB) is the only safe way to obtain liver tissue. However, it remains unclear whether successful sequencing of this extremely small and fragile tissue can be achieved for downstream characterization of the hepatic landscape. Methods: Here we leveraged in-house available single-cell RNA-sequencing (scRNA-seq) and single-nucleus (snRNA-seq) technologies and accompanying tissue processing protocols and performed an in-patient comparison on TJB's from decompensated cirrhosis patients (n = 3). Results: We confirmed a high concordance between nuclear and whole cell transcriptomes and captured 31,410 single nuclei and 6,152 single cells, respectively. The two platforms revealed similar diversity since all 8 major cell types could be identified, albeit with different cellular proportions thereof. Most importantly, hepatocytes were most abundant in snRNA-seq, while lymphocyte frequencies were elevated in scRNA-seq. We next focused our attention on hepatic myeloid cells due to their key role in injury and repair during chronic liver disease. Comparison of their transcriptional signatures indicated that these were largely overlapping between the two platforms. However, the scRNA-seq platform failed to recover sufficient Kupffer cell numbers, and other monocytes/macrophages featured elevated expression of stress-related parameters. Conclusion: Our results indicate that single-nucleus transcriptome sequencing provides an effective means to overcome complications associated with clinical specimen collection and could sufficiently profile all major hepatic cell types including all myeloid cell subsets. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Van Melkebeke, Verbeek, Bihary, Boesch, Boeckx, Feio-Azevedo, Smets, Wallays, Claus, Bonne, Maleux, Govaere, Korf, Lambrechts and van der Merwe.)
Databáze:	MEDLINE
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