Journal
DEVELOPMENTAL CELL
Volume 54, Issue 5, Pages 669-+Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2020.06.039
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Funding
- European Commission (GlycoSkin H2020-ERC)
- European Commission (Imgene H2O20)
- Lundbeck Foundation
- Danish Research Councils (Sapere Aude Research Leader grant)
- Danish National Research Foundation [DNRF107]
- Friis Foundation
- Michelsen Foundation
- A.P. Moller og Hustru Chastine Mc-Kinney Mollers Fond til Almene Formaal
- Danish Strategic Research Council
- University of Copenhagen [CDO2016]
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The glycome undergoes characteristic changes during histogenesis and organogenesis, but our understanding of the importance of select glycan structures for tissue formation and homeostasis is incomplete. Here, we present a human organotypic platform that allows genetic dissection of cellular glycosylation capacities and systematic interrogation of the roles of distinct glycan types in tissue formation. We used CRISPR-Cas9 gene targeting to generate a library of 3D organotypic skin tissues that selectively differ in their capacity to produce glycan structures on the main types of N- and O-linked glycoproteins and glycolipids. This tissue library revealed distinct changes in skin formation associated with a loss of features for all tested glycoconjugates. The organotypic skin model provides phenotypic cues for the distinct functions of glycoconjugates and serves as a unique resource for further genetic dissection and identification of the specific structural features involved. The strategy is also applicable to other organotypic tissue models.
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