Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model.
CRISPR/Cas9
Notch
epithelia
glycans
glycobiology
integrins
keratinocytes
organoid
organotypic model
skin
Journal
Developmental cell
ISSN: 1878-1551
Titre abrégé: Dev Cell
Pays: United States
ID NLM: 101120028
Informations de publication
Date de publication:
14 09 2020
14 09 2020
Historique:
received:
25
10
2019
revised:
07
04
2020
accepted:
29
06
2020
pubmed:
28
7
2020
medline:
24
2
2021
entrez:
26
7
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32710848
pii: S1534-5807(20)30547-5
doi: 10.1016/j.devcel.2020.06.039
pmc: PMC7497784
pii:
doi:
Substances chimiques
Glycoproteins
0
Polysaccharides
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
669-684.e7Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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