Cell atlas of the regenerating human liver after portal vein embolization

Agnieska Brazovskaja, Tomás Gomes (), Rene Holtackers, Philipp Wahle, Christiane Körner, Zhisong He, Theresa Schaffer, Julian Connor Eckel, René Hänsel, Malgorzata Santel, Makiko Seimiya, Timm Denecke, Michael Dannemann, Mario Brosch, Jochen Hampe, Daniel Seehofer, Georg Damm (), J. Gray Camp () and Barbara Treutlein ()
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Agnieska Brazovskaja: Max Planck Institute for Evolutionary Anthropology
Tomás Gomes: ETH Zürich
Rene Holtackers: ETH Zürich
Philipp Wahle: ETH Zürich
Christiane Körner: University Hospital, Leipzig University
Zhisong He: ETH Zürich
Theresa Schaffer: Max Planck Institute for Evolutionary Anthropology
Julian Connor Eckel: University Hospital, Leipzig University
René Hänsel: University Hospital, Leipzig University
Malgorzata Santel: ETH Zürich
Makiko Seimiya: ETH Zürich
Timm Denecke: Leipzig University
Michael Dannemann: Max Planck Institute for Evolutionary Anthropology
Mario Brosch: University Hospital Dresden, Technical University Dresden
Jochen Hampe: University Hospital Dresden, Technical University Dresden
Daniel Seehofer: University Hospital, Leipzig University
Georg Damm: University Hospital, Leipzig University
J. Gray Camp: Max Planck Institute for Evolutionary Anthropology
Barbara Treutlein: Max Planck Institute for Evolutionary Anthropology

Nature Communications, 2024, vol. 15, issue 1, 1-17

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-49236-7

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