Tissue geometry drives deterministic organoid patterning

• DOI: 10.1126/science.aaw9021
• Publication Date: 2022-01-06T18:56:16Z
• Authors: N. Gjorevski; M. Nikolaev; T. E. Brown; O. Mitrofanova; N. Brandenberg; F. W. DelRio; F. M. Yavitt; P. Liberali; K. S. Anseth; M. P. Lutolf
• Keywords: gradients; Paneth Cells; proliferation; Organogenesis; morphogenesis; Tissue Culture Techniques; intestinal stem-cell; Mice; crypt; coordinate; Animals; yap; Intestinal Mucosa; Cell Shape; Receptors, Notch; Tissue Engineering; Stem Cells; Cell Differentiation; Epithelial Cells; Hydrogels; YAP-Signaling Proteins; self-organization; 3. Good health; Organoids; yap/taz; epithelium; Signal Transduction

Spatial and temporal organoid control

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 et al . developed approaches for specifying the initial organoid geometry to build intestinal organoids of defined shape, size, and cell distributions, forming structures that are predictable, more similar to normal organs, and reproducible (see the Perspective by Huycke and Gartner). These methods identify symmetry-breaking mechanisms in intestinal morphogenesis and have potential for standardizing organoid-based therapies and facilitating the refinement of mechanistic studies. —BAP