Mucin-type O -glycosylation controls pluripotency in mouse embryonic stem cells via Wnt receptor endocytosis

• Published in: Journal of cell science Vol. 133; no. 20
• Main Authors: Pecori, Federico, Akimoto, Yoshihiro, Hanamatsu, Hisatoshi, Furukawa, Jun-Ichi, Shinohara, Yasuro, Ikehara, Yuzuru, Nishihara, Shoko
• Format: Journal Article
• Language: English
• Published: England 23.10.2020
• Subjects: Glycosylation; Wnt signaling pathway; C1GalT1; Embryonic stem cells; T antigen; Pluripotency
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.245845

Mouse embryonic stem cells (ESCs) can differentiate into a range of cell types during development, and this pluripotency is regulated by various extrinsic and intrinsic factors. Mucin-type -glycosylation has been suggested to be a potential factor in the control of ESC pluripotency, and is characterized by the addition of -acetylgalactosamine (GalNAc) to serine or threonine residues of membrane-anchored proteins and secreted proteins. To date, the relationship between mucin-type -glycosylation and signaling in ESCs remains undefined. Here, we identify the elongation pathway via C1GalT1 that synthesizes T antigen (Galβ1-3GalNAc) as the most prominent among mucin-type -glycosylation modifications in ESCs. Moreover, we show that mucin-type -glycosylation on the Wnt signaling receptor frizzled-5 (Fzd5) regulates its endocytosis via galectin-3 binding to T antigen, and that reduction of T antigen results in the exit of the ESCs from pluripotency via canonical Wnt signaling activation. Our findings reveal a novel regulatory mechanism that modulates Wnt signaling and, consequently, ESC pluripotency.This article has an associated First Person interview with the first author of the paper.