In a new Science study, researchers report the use of multiple bioengineering strategies to generate more structurally complex and reproducible intestinal organoids. Learn more ⬇ SciencePerspective:
Stem cell–derived organoids form through self-organization and serve as models for organ development, function, and disease, with potential applications in drug development and personalized medicine. However, in the absence of external guidance, developmental processes are stochastic, resulting in variable end products that differ significantly from the native organ. Gjorevski.
These differences in cell shape lead to spatial heterogeneities in YAP mechanosensing/transduction and Notch signaling, which in turn specify “crypt”- and “villus”-like domains by localizing Paneth cell differentiation and suppressing stem cell fates, respectively. Spatial variations in cell morphology dictated by tissue geometry thus render a normally random process highly stereotypical.
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