Creation of bladder assembloids mimicking tissue regeneration and cancer

Eunjee Kim, Seoyoung Choi, Byunghee Kang, Jung Ho Kong, Yubin Kim, Woong Hee Yoon, Hwa Rim Lee, Sung Eun Kim, Hyo Min Kim, Hye Sun Lee, Chorong Yang, You Jeong Lee, Minyong Kang, Tae Young Roh, Sungjune Jung, Sanguk Kim, Ja Hyeon Ku, Kunyoo Shin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)664-669
Number of pages6
JournalNature
Volume588
Issue number7839
DOIs
StatePublished - Dec 24 2020

ASJC Scopus subject areas

  • General

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