IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51487-3.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51487-3
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-51487-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. 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.
    2. 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.
    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Delilah Hendriks & Benedetta Artegiani & Thanasis Margaritis & Iris Zoutendijk & Susana Chuva de Sousa Lopes & Hans Clevers, 2024. "Mapping of mitogen and metabolic sensitivity in organoids defines requirements for human hepatocyte growth," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Franziska Hildebrandt & Alma Andersson & Sami Saarenpää & Ludvig Larsson & Noémi Van Hul & Sachie Kanatani & Jan Masek & Ewa Ellis & Antonio Barragan & Annelie Mollbrink & Emma R. Andersson & Joakim L, 2021. "Spatial Transcriptomics to define transcriptional patterns of zonation and structural components in the mouse liver," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Yang Liu & Qi Chen & Hyun-Woo Jeong & Bong Ihn Koh & Emma C. Watson & Cong Xu & Martin Stehling & Bin Zhou & Ralf H. Adams, 2022. "A specialized bone marrow microenvironment for fetal haematopoiesis," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    4. Bani Mukhopadhyay & Cheryl Marietta & Pei-Hong Shen & Abdul Oiseni & Faridoddin Mirshahi & Maria Mazzu & Colin Hodgkinson & Eli Winkler & Qiaoping Yuan & Daniel Miranda & George Kunos & Arun J. Sanyal, 2024. "A patient-based iPSC-derived hepatocyte model of alcohol-associated cirrhosis reveals bioenergetic insights into disease pathogenesis," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    5. Akimichi Inaba & Zewen Kelvin Tuong & Tian X. Zhao & Andrew P. Stewart & Rebeccah Mathews & Lucy Truman & Rouchelle Sriranjan & Jane Kennet & Kourosh Saeb-Parsy & Linda Wicker & Frank Waldron-Lynch & , 2023. "Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    6. James T. Topham & Erica S. Tsang & Joanna M. Karasinska & Andrew Metcalfe & Hassan Ali & Steve E. Kalloger & Veronika Csizmok & Laura M. Williamson & Emma Titmuss & Karina Nielsen & Gian Luca Negri & , 2022. "Integrative analysis of KRAS wildtype metastatic pancreatic ductal adenocarcinoma reveals mutation and expression-based similarities to cholangiocarcinoma," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    7. Ondrej Suchanek & John R. Ferdinand & Zewen K. Tuong & Sathi Wijeyesinghe & Anita Chandra & Ann-Katrin Clauder & Larissa N. Almeida & Simon Clare & Katherine Harcourt & Christopher J. Ward & Rachael B, 2023. "Tissue-resident B cells orchestrate macrophage polarisation and function," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    8. Jing Qi & Yang Zhou & Zicen Zhao & Shuilin Jin, 2021. "SDImpute: A statistical block imputation method based on cell-level and gene-level information for dropouts in single-cell RNA-seq data," PLOS Computational Biology, Public Library of Science, vol. 17(6), pages 1-20, June.
    9. Aleksandr Ianevski & Anil K. Giri & Tero Aittokallio, 2022. "Fully-automated and ultra-fast cell-type identification using specific marker combinations from single-cell transcriptomic data," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    10. Wenwei Sun & Meimei Wang & Jun Zhao & Shuang Zhao & Wenchao Zhu & Xiaoting Wu & Feifei Li & Wei Liu & Zhuo Wang & Meng Gao & Yiyue Zhang & Jin Xu & Meijia Zhang & Qiang Wang & Zilong Wen & Juan Shen &, 2023. "Sulindac selectively induces autophagic apoptosis of GABAergic neurons and alters motor behaviour in zebrafish," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Shanshan Guo & Yonghao Feng & Xiaopeng Zhu & Xinyi Zhang & Hui Wang & Ruwen Wang & Qiongyue Zhang & Yiming Li & Yan Ren & Xin Gao & Hua Bian & Tiemin Liu & Huanqing Gao & Xingxing Kong, 2023. "Metabolic crosstalk between skeletal muscle cells and liver through IRF4-FSTL1 in nonalcoholic steatohepatitis," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    12. Joachim Jonghe & Tomasz S. Kaminski & David B. Morse & Marcin Tabaka & Anna L. Ellermann & Timo N. Kohler & Gianluca Amadei & Charlotte E. Handford & Gregory M. Findlay & Magdalena Zernicka-Goetz & Sa, 2023. "spinDrop: a droplet microfluidic platform to maximise single-cell sequencing information content," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    13. Kim Vanuytsel & Carlos Villacorta-Martin & Jonathan Lindstrom-Vautrin & Zhe Wang & Wilfredo F. Garcia-Beltran & Vladimir Vrbanac & Dylan Parsons & Evan C. Lam & Taylor M. Matte & Todd W. Dowrey & Sara, 2022. "Multi-modal profiling of human fetal liver hematopoietic stem cells reveals the molecular signature of engraftment," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    14. Jie Liao & Jingyang Qian & Yin Fang & Zhuo Chen & Xiang Zhuang & Ningyu Zhang & Xin Shao & Yining Hu & Penghui Yang & Junyun Cheng & Yang Hu & Lingqi Yu & Haihong Yang & Jinlu Zhang & Xiaoyan Lu & Li , 2022. "De novo analysis of bulk RNA-seq data at spatially resolved single-cell resolution," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    15. Yuan Liao & Lifeng Ma & Qile Guo & Weigao E & Xing Fang & Lei Yang & Fanwei Ruan & Jingjing Wang & Peijing Zhang & Zhongyi Sun & Haide Chen & Zhongliang Lin & Xueyi Wang & Xinru Wang & Huiyu Sun & Xiu, 2022. "Cell landscape of larval and adult Xenopus laevis at single-cell resolution," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    16. Clara Alsinet & Maria Nascimento Primo & Valentina Lorenzi & Erica Bello & Iva Kelava & Carla P. Jones & Roser Vilarrasa-Blasi & Carmen Sancho-Serra & Andrew J. Knights & Jong-Eun Park & Beata S. Wysp, 2022. "Robust temporal map of human in vitro myelopoiesis using single-cell genomics," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    17. Jake R. Thomas & Anna Appios & Emily F. Calderbank & Nagisa Yoshida & Xiaohui Zhao & Russell S. Hamilton & Ashley Moffett & Andrew Sharkey & Elisa Laurenti & Courtney W. Hanna & Naomi McGovern, 2023. "Primitive haematopoiesis in the human placenta gives rise to macrophages with epigenetically silenced HLA-DR," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Inmaculada Ruz-Maldonado & John T. Gonzalez & Hanming Zhang & Jonathan Sun & Alicia Bort & Inamul Kabir & Richard G. Kibbey & Yajaira Suárez & Daniel M. Greif & Carlos Fernández-Hernando, 2024. "Heterogeneity of hepatocyte dynamics restores liver architecture after chemical, physical or viral damage," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    19. Mingze Gao & Chen Qiao & Yuanhua Huang, 2022. "UniTVelo: temporally unified RNA velocity reinforces single-cell trajectory inference," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    20. T. Hautz & S. Salcher & M. Fodor & G. Sturm & S. Ebner & A. Mair & M. Trebo & G. Untergasser & S. Sopper & B. Cardini & A. Martowicz & J. Hofmann & S. Daum & M. Kalb & T. Resch & F. Krendl & A. Weisse, 2023. "Immune cell dynamics deconvoluted by single-cell RNA sequencing in normothermic machine perfusion of the liver," Nature Communications, Nature, vol. 14(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51487-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.