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Cell atlas of the regenerating human liver after portal vein embolization

Author

Listed:
  • 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
    Leipzig University)

  • Malgorzata Santel

    (ETH Zürich)

  • Makiko Seimiya

    (ETH Zürich)

  • Timm Denecke

    (Leipzig University)

  • Michael Dannemann

    (Max Planck Institute for Evolutionary Anthropology
    University of Tartu)

  • Mario Brosch

    (University Hospital Dresden, Technical University Dresden
    Technical University Dresden)

  • Jochen Hampe

    (University Hospital Dresden, Technical University 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
    Roche Pharma Research and Early Development, Roche Innovation Center Basel)

  • Barbara Treutlein

    (Max Planck Institute for Evolutionary Anthropology
    ETH Zürich)

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.

Suggested Citation

  • Agnieska Brazovskaja & Tomás Gomes & Rene Holtackers & Philipp Wahle & Christiane Körner & Zhisong He & Theresa Schaffer & Julian Connor Eckel & René Hänsel & Malgorzata Santel & Makiko Seimiya & Timm, 2024. "Cell atlas of the regenerating human liver after portal vein embolization," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49236-7
    DOI: 10.1038/s41467-024-49236-7
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    1. Sonya A. MacParland & Jeff C. Liu & Xue-Zhong Ma & Brendan T. Innes & Agata M. Bartczak & Blair K. Gage & Justin Manuel & Nicholas Khuu & Juan Echeverri & Ivan Linares & Rahul Gupta & Michael L. Cheng, 2018. "Single cell RNA sequencing of human liver reveals distinct intrahepatic macrophage populations," Nature Communications, Nature, vol. 9(1), pages 1-21, December.
    2. Keren Bahar Halpern & Rom Shenhav & Orit Matcovitch-Natan & Beáta Tóth & Doron Lemze & Matan Golan & Efi E. Massasa & Shaked Baydatch & Shanie Landen & Andreas E. Moor & Alexander Brandis & Amir Gilad, 2017. "Single-cell spatial reconstruction reveals global division of labour in the mammalian liver," Nature, Nature, vol. 542(7641), pages 352-356, February.
    3. Kyle J. Travaglini & Ahmad N. Nabhan & Lolita Penland & Rahul Sinha & Astrid Gillich & Rene V. Sit & Stephen Chang & Stephanie D. Conley & Yasuo Mori & Jun Seita & Gerald J. Berry & Joseph B. Shrager , 2020. "A molecular cell atlas of the human lung from single-cell RNA sequencing," Nature, Nature, vol. 587(7835), pages 619-625, November.
    4. Nadim Aizarani & Antonio Saviano & Sagar & Laurent Mailly & Sarah Durand & Josip S. Herman & Patrick Pessaux & Thomas F. Baumert & Dominic Grün, 2019. "A human liver cell atlas reveals heterogeneity and epithelial progenitors," Nature, Nature, vol. 572(7768), pages 199-204, August.
    5. Bi-Sen Ding & Daniel J. Nolan & Jason M. Butler & Daylon James & Alexander O. Babazadeh & Zev Rosenwaks & Vivek Mittal & Hideki Kobayashi & Koji Shido & David Lyden & Thomas N. Sato & Sina Y. Rabbany , 2010. "Inductive angiocrine signals from sinusoidal endothelium are required for liver regeneration," Nature, Nature, vol. 468(7321), pages 310-315, November.
    6. Bojan Losic & Amanda J. Craig & Carlos Villacorta-Martin & Sebastiao N. Martins-Filho & Nicholas Akers & Xintong Chen & Mehmet E. Ahsen & Johann Felden & Ismail Labgaa & Delia DʹAvola & Kimaada Allett, 2020. "Intratumoral heterogeneity and clonal evolution in liver cancer," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    7. J. Gray Camp & Keisuke Sekine & Tobias Gerber & Henry Loeffler-Wirth & Hans Binder & Malgorzata Gac & Sabina Kanton & Jorge Kageyama & Georg Damm & Daniel Seehofer & Lenka Belicova & Marc Bickle & Ric, 2017. "Multilineage communication regulates human liver bud development from pluripotency," Nature, Nature, vol. 546(7659), pages 533-538, June.
    8. Keren Bahar Halpern & Rom Shenhav & Orit Matcovitch-Natan & Beáta Tóth & Doron Lemze & Matan Golan & Efi E. Massasa & Shaked Baydatch & Shanie Landen & Andreas E. Moor & Alexander Brandis & Amir Gilad, 2017. "Erratum: Single-cell spatial reconstruction reveals global division of labour in the mammalian liver," Nature, Nature, vol. 543(7647), pages 742-742, March.
    9. Takanori Takebe & Keisuke Sekine & Masahiro Enomura & Hiroyuki Koike & Masaki Kimura & Takunori Ogaeri & Ran-Ran Zhang & Yasuharu Ueno & Yun-Wen Zheng & Naoto Koike & Shinsuke Aoyama & Yasuhisa Adachi, 2013. "Vascularized and functional human liver from an iPSC-derived organ bud transplant," Nature, Nature, vol. 499(7459), pages 481-484, July.
    10. Mario Brosch & Kathrin Kattler & Alexander Herrmann & Witigo von Schönfels & Karl Nordström & Daniel Seehofer & Georg Damm & Thomas Becker & Sebastian Zeissig & Sophie Nehring & Fabian Reichel & Vince, 2018. "Epigenomic map of human liver reveals principles of zonated morphogenic and metabolic control," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    11. Dorin-Mirel Popescu & Rachel A. Botting & Emily Stephenson & Kile Green & Simone Webb & Laura Jardine & Emily F. Calderbank & Krzysztof Polanski & Issac Goh & Mirjana Efremova & Meghan Acres & Daniel , 2019. "Decoding human fetal liver haematopoiesis," Nature, Nature, vol. 574(7778), pages 365-371, October.
    12. P. Ramachandran & R. Dobie & J. R. Wilson-Kanamori & E. F. Dora & B. E. P. Henderson & N. T. Luu & J. R. Portman & K. P. Matchett & M. Brice & J. A. Marwick & R. S. Taylor & M. Efremova & R. Vento-Tor, 2019. "Resolving the fibrotic niche of human liver cirrhosis at single-cell level," Nature, Nature, vol. 575(7783), pages 512-518, November.
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