Page 6 - R. Organoid
P. 6
[R. Organoid-3]
Three-dimensional reconstitution of bladder assembloids that
structurally and functionally recapitulate in vivo tissue
regeneration and cancer
Eunjee Kim¹, Yubin Kim¹, Seoyoung Choi¹, SungEun Kim¹, Kunyoo Shin¹
¹Life Sciences, POSTECH, Pohang 37673, 대한민국
Current organoid models are limited by their inability to mimic mature organ architecture and associated tissue
microenvironments. Here, we create multi-layer 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.
As a malignant counterpart, tumor assembloids are also developed to recapitulate the in vivo pathophysiological
features of patient-derived urothelial carcinoma. Using the genetically manipulated tumor assembloid platform, we
identify tumoral FOXA1, induced by stromal BMP, as a master pioneering factor driving enhancer reprogramming
for the determination of tumor phenotype, suggesting the importance of the FOXA1–BMP–HH signaling feedback
axis between tumor and stroma in the control of tumor plasticity.
