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Spatiotemporal Gradient and Instability of Wnt Induce Heterogeneous Growth and Differentiation of Human Intestinal Organoids

Authors
 Woojung Shin  ;  Alexander Wu  ;  Soyoun Min  ;  Yong Cheol Shin  ;  R Y Declan Fleming  ;  S Gail Eckhardt  ;  Hyun Jung Kim 
Citation
 ISCIENCE, Vol.23(8) : 101372, 2020-08 
Journal Title
ISCIENCE
Issue Date
2020-08
Keywords
Cancer ; Computer Modeling ; Tissue Engineering
Abstract
In a conventional culture of three-dimensional human intestinal organoids, extra-cellular matrix hydrogel has been used to provide a physical space for the growth and morphogenesis of organoids in the presence of exogenous morphogens such as Wnt3a. We found that organoids embedded in a dome-shaped hydrogel show significant size heterogeneity in different locations inside the hydrogel. Computational simulations revealed that the instability and diffusion limitation of Wnt3a constitutively generate a concentration gradient inside the hydrogel. The location-dependent heterogeneity of organoids in a hydrogel dome substantially perturbed the transcriptome profile associated with epithelial functions, cytodifferentiation including mucin 2 expression, and morphological characteristics. This heterogeneous phenotype was significantly mitigated when the Wnt3a was frequently replenished in the culture medium. Our finding suggests that the morphological, transcriptional, translational, and functional heterogeneity in conventional organoid cultures may lead to a false interpretation of the experimental results in organoid-based studies.
Files in This Item:
T9992020248.pdf Download
DOI
10.1016/j.isci.2020.101372
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Medical Engineering (의학공학교실) > 1. Journal Papers
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190026
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