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Generation of human iPSC-derived 3D bile duct within liver organoid by incorporating human iPSC-derived blood vessel

Author

Listed:
  • Erica Carolina

    (The University of Tokyo
    The University of Tokyo)

  • Yoshiki Kuse

    (The University of Tokyo)

  • Ayumu Okumura

    (The University of Tokyo
    The University of Tokyo)

  • Kenji Aoshima

    (The University of Tokyo
    The University of Tokyo)

  • Tomomi Tadokoro

    (Yokohama City University Graduate School of Medicine)

  • Shinya Matsumoto

    (The University of Tokyo)

  • Eriko Kanai

    (The University of Tokyo)

  • Takashi Okumura

    (The University of Tokyo)

  • Toshiharu Kasai

    (The University of Tokyo)

  • Souichiro Yamabe

    (The University of Tokyo
    The University of Tokyo)

  • Yuji Nishikawa

    (Asahikawa Medical University)

  • Kiyoshi Yamaguchi

    (The University of Tokyo)

  • Yoichi Furukawa

    (The University of Tokyo)

  • Naoki Tanimizu

    (The University of Tokyo)

  • Hideki Taniguchi

    (The University of Tokyo
    Yokohama City University Graduate School of Medicine)

Abstract

In fetal development, tissue interaction such as the interplay between blood vessel (BV) and epithelial tissue is crucial for organogenesis. Here we recapitulate the spatial arrangement between liver epithelial tissue and the portal vein to observe the formation of intrahepatic bile ducts (BDs) from human induced pluripotent stem cells (hiPSC). We co-culture hiPSC-liver progenitors on the artificial BV consisting of immature smooth muscle cells and endothelial cells, both derived from hiPSCs. After 3 weeks, liver progenitors within hiPSC-BV-incorporated liver organoids (BVLO) differentiate to cholangiocytes and acquire epithelial characteristics, including intercellular junctions, microvilli on the apical membrane, and secretory functions. Furthermore, liver surface transplanted-BVLO temporarily attenuates cholestatic injury symptoms. Single cell RNA sequence analysis suggests that BD interact with the BV in BVLO through TGFβ and Notch pathways. Knocking out JAG1 in hiPSC-BV significantly attenuates bile duct formation, highlighting BVLO potential as a model for Alagille syndrome, a congenital biliary disease. Overall, we develop a novel 3D co-culture method that successfully establishes functional human BDs by emulating liver epithelial-BV interaction.

Suggested Citation

  • Erica Carolina & Yoshiki Kuse & Ayumu Okumura & Kenji Aoshima & Tomomi Tadokoro & Shinya Matsumoto & Eriko Kanai & Takashi Okumura & Toshiharu Kasai & Souichiro Yamabe & Yuji Nishikawa & Kiyoshi Yamag, 2024. "Generation of human iPSC-derived 3D bile duct within liver organoid by incorporating human iPSC-derived blood vessel," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51487-3
    DOI: 10.1038/s41467-024-51487-3
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    References listed on IDEAS

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    1. 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.
    2. 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.
    3. 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.
    4. 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.
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