| Literature DB >> 33328632 |
Eunjee Kim1, Seoyoung Choi1, Byunghee Kang1,2, JungHo Kong1, Yubin Kim1, Woong Hee Yoon2, Hwa-Rim Lee3, SungEun Kim1, Hyo-Min Kim1,2, HyeSun Lee4, Chorong Yang2, You Jeong Lee2, Minyong Kang5,6,7, Tae-Young Roh8,9, Sungjune Jung2,3, Sanguk Kim1, Ja Hyeon Ku10, Kunyoo Shin11.
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.Entities:
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Year: 2020 PMID： 33328632 DOI： 10.1038/s41586-020-3034-x
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962