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Creation of bladder assembloids mimicking tissue regeneration and cancer

机译：模拟组织再生和癌症的膀胱组合的创建

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摘要

Current organoid models are limited by their inability to mimic mature organ architecture and associated tissue microenvironments~(1,2). 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.
机译：目前的有机体模型受到它们无法模仿成熟器官结构和相关的组织微环境〜（1,2）的限制。在这里，我们通过将组织干细胞与基质成分重构组织干细胞来创造多层膀胱'组件，以表示具有周围的基质上皮和外部肌肉层的有组织的结构。这些组合物在单细胞转录组水平的细胞组成和基因表达中表现出成熟成年膀胱的特征，并在对损伤的再生反应的体内组织动力学中概括。我们还开发恶性对手肿瘤组件，以重新提出尿路上皮癌的体内病理生理学特征。使用基因操纵的肿瘤组件平台，我们鉴定由基质骨形态发生蛋白（BMP）诱导的巨曲线FOXA1，作为推动增强剂进行肿瘤表型重新编程的母先驱因素，表明FOXA1-BMP-Hedgehog的重要性肿瘤塑性控制中肿瘤与基质之间的信号反馈轴。

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  • 来源
    《Nature》 |2020年第7839期|664-669|共6页
  • 作者

    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 Roh; Sungjune Jung; Sanguk Kim; Ja Hyeon Ku; Kunyoo Shin;

  • 作者单位

    Department of Life Sciences Pohang University of Science and Technology;

    Department of Life Sciences Pohang University of Science and Technology;

    Department of Life Sciences Pohang University of Science and Technology|Department of Integrative Biosciences and Biotechnology Pohang University of Science and Technology;

    Department of Life Sciences Pohang University of Science and Technology;

    Department of Life Sciences Pohang University of Science and Technology;

    Department of Integrative Biosciences and Biotechnology Pohang University of Science and Technology;

    Department of Creative IT Engineering Pohang University of Science and Technology;

    Department of Life Sciences Pohang University of Science and Technology;

    Department of Life Sciences Pohang University of Science and Technology|Department of Integrative Biosciences and Biotechnology Pohang University of Science and Technology;

    Department of Urology Seoul National University Hospital;

    Department of Integrative Biosciences and Biotechnology Pohang University of Science and Technology;

    Department of Integrative Biosciences and Biotechnology Pohang University of Science and Technology;

    Department of Urology Samsung Medical Center Sungkyunkwan University School of Medicine|Department of Health Sciences and Technology SAIHST Sungkyunkwan University|Department of Digital Health SAIHST Sungkyunkwan University;

    Department of Life Sciences Pohang University of Science and Technology|Department of Integrative Biosciences and Biotechnology Pohang University of Science and Technology;

    Department of Integrative Biosciences and Biotechnology Pohang University of Science and Technology|Department of Creative IT Engineering Pohang University of Science and Technology;

    Department of Life Sciences Pohang University of Science and Technology;

    Department of Urology Seoul National University Hospital;

    Department of Life Sciences Pohang University of Science and Technology;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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