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Creation of bladder assembloids mimicking tissue regeneration and cancer

Author

Listed:
  • Eunjee Kim

    (Pohang University of Science and Technology)

  • Seoyoung Choi

    (Pohang University of Science and Technology)

  • Byunghee Kang

    (Pohang University of Science and Technology
    Pohang University of Science and Technology)

  • JungHo Kong

    (Pohang University of Science and Technology)

  • Yubin Kim

    (Pohang University of Science and Technology)

  • Woong Hee Yoon

    (Pohang University of Science and Technology)

  • Hwa-Rim Lee

    (Pohang University of Science and Technology)

  • SungEun Kim

    (Pohang University of Science and Technology)

  • Hyo-Min Kim

    (Pohang University of Science and Technology
    Pohang University of Science and Technology)

  • HyeSun Lee

    (Seoul National University Hospital)

  • Chorong Yang

    (Pohang University of Science and Technology)

  • You Jeong Lee

    (Pohang University of Science and Technology)

  • Minyong Kang

    (Sungkyunkwan University School of Medicine
    Sungkyunkwan University
    SAIHST, Sungkyunkwan University)

  • Tae-Young Roh

    (Pohang University of Science and Technology
    Pohang University of Science and Technology)

  • Sungjune Jung

    (Pohang University of Science and Technology
    Pohang University of Science and Technology)

  • Sanguk Kim

    (Pohang University of Science and Technology)

  • Ja Hyeon Ku

    (Seoul National University Hospital)

  • Kunyoo Shin

    (Pohang University of Science and Technology)

Abstract

Current organoid models are limited by their inability to mimic mature organ architecture and associated tissue microenvironments1,2. Here we create multilayer bladder ‘assembloids’ by reconstituting tissue stem cells with stromal components to represent an organized architecture with an epithelium surrounding stroma and an outer muscle layer. These assembloids exhibit characteristics of mature adult bladders in cell composition and gene expression at the single-cell transcriptome level, and recapitulate in vivo tissue dynamics of regenerative responses to injury. We also develop malignant counterpart tumour assembloids to recapitulate the in vivo pathophysiological features of urothelial carcinoma. Using the genetically manipulated tumour-assembloid platform, we identify tumoural FOXA1, induced by stromal bone morphogenetic protein (BMP), as a master pioneer factor that drives enhancer reprogramming for the determination of tumour phenotype, suggesting the importance of the FOXA1–BMP–hedgehog signalling feedback axis between tumour and stroma in the control of tumour plasticity.

Suggested Citation

  • Eunjee Kim & Seoyoung Choi & Byunghee Kang & JungHo Kong & Yubin Kim & Woong Hee Yoon & Hwa-Rim Lee & SungEun Kim & Hyo-Min Kim & HyeSun Lee & Chorong Yang & You Jeong Lee & Minyong Kang & Tae-Young R, 2020. "Creation of bladder assembloids mimicking tissue regeneration and cancer," Nature, Nature, vol. 588(7839), pages 664-669, December.
    • Handle: RePEc:nat:nature:v:588:y:2020:i:7839:d:10.1038_s41586-020-3034-x
    DOI: 10.1038/s41586-020-3034-x
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    Cited by:

    1. Yanmei Zhang & Qifan Hu & Yuquan Pei & Hao Luo & Zixuan Wang & Xinxin Xu & Qing Zhang & Jianli Dai & Qianqian Wang & Zilian Fan & Yongcong Fang & Min Ye & Binhan Li & Mailin Chen & Qi Xue & Qingfeng Z, 2024. "A patient-specific lung cancer assembloid model with heterogeneous tumor microenvironments," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    2. Manqiang Lin & Kimberly Hartl & Julian Heuberger & Giulia Beccaceci & Hilmar Berger & Hao Li & Lichao Liu & Stefanie Müllerke & Thomas Conrad & Felix Heymann & Andrew Woehler & Frank Tacke & Nikolaus , 2023. "Establishment of gastrointestinal assembloids to study the interplay between epithelial crypts and their mesenchymal niche," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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