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Publication : Creation of bladder assembloids mimicking tissue regeneration and cancer.

First Author  Kim E Year  2020
Journal  Nature Volume  588
Issue  7839 Pages  664-669
PubMed ID  33328632 Mgi Jnum  J:300306
Mgi Id  MGI:6492433 Doi  10.1038/s41586-020-3034-x
Citation  Kim E, et al. (2020) Creation of bladder assembloids mimicking tissue regeneration and cancer. Nature 588(7839):664-669
abstractText  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.
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