%0 Journal Article
%T Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.
%A Dabelsteen S
%A Pallesen EMH
%A Marinova IN
%A Nielsen MI
%A Adamopoulou M
%A Rømer TB
%A Levann A
%A Andersen MM
%A Ye Z
%A Thein D
%A Bennett EP
%A Büll C
%A Moons SJ
%A Boltje T
%A Clausen H
%A Vakhrushev SY
%A Bagdonaite I
%A Wandall HH
%J Dev Cell
%V 54
%N 5
%D 09 2020 14
%M 32710848
%F 13.417
%R 10.1016/j.devcel.2020.06.039
%X 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.