Essential functions of glycans in human epithelia dissected by a CRISPR/Cas9-engineered human organotypic skin model

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 Nand 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.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Keratinocyte, Skin

SUBMITTER: Sergey Vakhrushev  

LAB HEAD: Sergey Vakhrushev

PROVIDER: PXD018418 | Pride | 2021-09-09

REPOSITORIES: Pride