Creation of bladder assembloids mimicking tissue regeneration and cancer

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 () and Kunyoo Shin ()
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Eunjee Kim: Pohang University of Science and Technology
Seoyoung Choi: Pohang University of Science and Technology
Byunghee Kang: 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
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
Tae-Young Roh: Pohang University of Science and Technology
Sungjune Jung: 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

Nature, 2020, vol. 588, issue 7839, 664-669

Abstract: 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.

Date: 2020
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DOI: 10.1038/s41586-020-3034-x

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