Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model
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Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model. / Dabelsteen, Sally; Pallesen, Emil M. H.; Marinova, Irina N.; Nielsen, Mathias I.; Adamopoulou, Maria; Rømer, Troels B.; Levann, Asha; Andersen, Mikkel M.; Ye, Zilu; Thein, David; Bennett, Eric P; Büll, Christian; Moons, Sam J.; Boltje, Thomas; Clausen, Henrik; Vakhrushev, Sergey Y.; Bagdonaite, Ieva; Wandall, Hans H.
I: Developmental Cell, Bind 54, Nr. 5, 2020, s. 669-684.e7.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Essential Functions of Glycans in Human Epithelia Dissected by a CRISPR-Cas9-Engineered Human Organotypic Skin Model
AU - Dabelsteen, Sally
AU - Pallesen, Emil M. H.
AU - Marinova, Irina N.
AU - Nielsen, Mathias I.
AU - Adamopoulou, Maria
AU - Rømer, Troels B.
AU - Levann, Asha
AU - Andersen, Mikkel M.
AU - Ye, Zilu
AU - Thein, David
AU - Bennett, Eric P
AU - Büll, Christian
AU - Moons, Sam J.
AU - Boltje, Thomas
AU - Clausen, Henrik
AU - Vakhrushev, Sergey Y.
AU - Bagdonaite, Ieva
AU - Wandall, Hans H.
PY - 2020
Y1 - 2020
N2 - 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.
AB - 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.
U2 - 10.1016/j.devcel.2020.06.039
DO - 10.1016/j.devcel.2020.06.039
M3 - Journal article
C2 - 32710848
VL - 54
SP - 669-684.e7
JO - Developmental Cell
JF - Developmental Cell
SN - 1534-5807
IS - 5
ER -
ID: 245659289