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Science. 2018 Jul 13;361(6398):156-162. doi: 10.1126/science.aat0271. Epub 2018 May 31.

Programming self-organizing multicellular structures with synthetic cell-cell signaling.

Author information

1
Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, and Center for Systems and Synthetic Biology, University of California, San Francisco, CA 94158, USA.
2
Department of Mechanical Engineering, Stanford University, Stanford, CA 94305, USA.
3
Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, and Center for Systems and Synthetic Biology, University of California, San Francisco, CA 94158, USA. leonardo.morsut@med.usc.edu wendell.lim@ucsf.edu.
4
Present address: Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, University of Southern California, Los Angeles, CA 90033, USA.

Abstract

A common theme in the self-organization of multicellular tissues is the use of cell-cell signaling networks to induce morphological changes. We used the modular synNotch juxtacrine signaling platform to engineer artificial genetic programs in which specific cell-cell contacts induced changes in cadherin cell adhesion. Despite their simplicity, these minimal intercellular programs were sufficient to yield assemblies with hallmarks of natural developmental systems: robust self-organization into multidomain structures, well-choreographed sequential assembly, cell type divergence, symmetry breaking, and the capacity for regeneration upon injury. The ability of these networks to drive complex structure formation illustrates the power of interlinking cell signaling with cell sorting: Signal-induced spatial reorganization alters the local signals received by each cell, resulting in iterative cycles of cell fate branching. These results provide insights into the evolution of multicellularity and demonstrate the potential to engineer customized self-organizing tissues or materials.

PMID:
29853554
PMCID:
PMC6492944
DOI:
10.1126/science.aat0271
[Indexed for MEDLINE]
Free PMC Article

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