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Journal Article

Cell atlas of the regenerating human liver after portal vein embolization

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Brazovskaja,  Agnieška       
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Schaffer,  Theresa       
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Dannemann,  Michael       
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Camp,  J. Gray
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Treutlein,  Barbara       
Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Max Planck Society;

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Fulltext (public)

Brazovskaja_Cell_NatComm_2024.pdf
(Publisher version), 5MB

Supplementary Material (public)

Brazovskaja_Cell_NatComm_Suppl_2024.pdf
(Supplementary material), 21MB

Citation

Brazovskaja, A., Gomes, T., Holtackers, R., Wahle, P., Körner, C., He, Z., et al. (2024). Cell atlas of the regenerating human liver after portal vein embolization. Nature Communications, 15: 5827. doi:10.1038/s41467-024-49236-7.


Cite as: https://hdl.handle.net/21.11116/0000-000F-9A24-B
Abstract
The liver has the remarkable capacity to regenerate. In the clinic, regeneration is induced by portal vein embolization, which redirects portal blood flow, resulting in liver hypertrophy in locations with increased blood supply, and atrophy of embolized segments. Here, we apply single-cell and single-nucleus transcriptomics on healthy, hypertrophied, and atrophied patient-derived liver samples to explore cell states in the regenerating liver. Our data unveils pervasive upregulation of genes associated with developmental processes, cellular adhesion, and inflammation in post-portal vein embolization liver, disrupted portal-central hepatocyte zonation, and altered cell subtype composition of endothelial and immune cells. Interlineage crosstalk analysis reveals mesenchymal cells as an interaction hub between immune and endothelial cells, and highlights the importance of extracellular matrix proteins in liver regeneration. Moreover, we establish tissue-scale iterative indirect immunofluorescence imaging for high-dimensional spatial analysis of perivascular microenvironments, uncovering changes to tissue architecture in regenerating liver lobules. Altogether, our data is a rich resource revealing cellular and histological changes in human liver regeneration.