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research article

Tissue geometry drives deterministic organoid patterning

Gjorevski, N.  
•
Nikolaev, M.  
•
Brown, T. E.
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January 7, 2022
Science

Epithelial organoids are stem cell-derived tissues that approximate aspects of real organs, and thus they have potential as powerful tools in basic and translational research. By definition, they self-organize, but the structures formed are often heterogeneous and irreproducible, which limits their use in the lab and clinic. We describe methodologies for spatially and temporally controlling organoid formation, thereby rendering a stochastic process more deterministic. Bioengineered stem cell microenvironments are used to specify the initial geometry of intestinal organoids, which in turn controls their patterning and crypt formation. We leveraged the reproducibility and predictability of the culture to identify the underlying mechanisms of epithelial patterning, which may contribute to reinforcing intestinal regionalization in vivo. By controlling organoid culture, we demonstrate how these structures can be used to answer questions not readily addressable with the standard, more variable, organoid models.

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Type
research article
DOI
10.1126/science.aaw9021
Web of Science ID

WOS:000740261400034

Author(s)
Gjorevski, N.  
Nikolaev, M.  
Brown, T. E.
Mitrofanova, O.  
Brandenberg, N.  
DelRio, F. W.
Yavitt, F. M.
Liberali, P.
Anseth, K. S.
Lutolf, M. P.  
Date Issued

2022-01-07

Publisher

American Association for the Advancement of Science

Published in
Science
Volume

375

Issue

6576

Article Number

eaaw9021

Start page

40

Subjects

Multidisciplinary Sciences

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Science & Technology - Other Topics

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intestinal stem-cell

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self-organization

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crypt

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yap

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yap/taz

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proliferation

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morphogenesis

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coordinate

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epithelium

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gradients

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

Available on Infoscience
February 28, 2022
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/185887
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