{Reference Type}: Journal Article
{Title}: Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.
{Author}: Dabelsteen S;Pallesen EMH;Marinova IN;Nielsen MI;Adamopoulou M;Rømer TB;Levann A;Andersen MM;Ye Z;Thein D;Bennett EP;Büll C;Moons SJ;Boltje T;Clausen H;Vakhrushev SY;Bagdonaite I;Wandall HH;
{Journal}: Dev Cell
{Volume}: 54
{Issue}: 5
{Year}: 09 2020 14
{Factor}: 13.417
{DOI}: 10.1016/j.devcel.2020.06.039
{Abstract}: 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.