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Cell recognition molecule L1 promotes embryonic stem cell differentiation through the regulation of cell surface glycosylation
Authors:Ying Li  Xiaohua Huang  Yue An  Feng Ren  Zara Zhuyun Yang  Hongmei Zhu  Lei Zhou  Xiaowen He  Melitta Schachner  Zhicheng Xiao  Keli Ma  Yali Li
Institution:1. Department of Biochemistry and Molecular Biology, Dalian Medical University, Dalian 116044, China;2. Department of Clinical Laboratory, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China;3. Department of Clinical Biochemistry, College of Laboratory Medicine, Dalian Medical University, Dalian 116044, China;4. The Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Molecular and Clinical Medicine, Kunming Medical University, Kunming 650228, China;5. Department of Anatomy and Developmental Biology, Monash University, Clayton 3800, Australia;6. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers University, New Brunswick, NJ, United States;g Department of Anatomy, National University of Singapore, Singapore 119078, Singapore
Abstract:Cell recognition molecule L1 (CD171) plays an important role in neuronal survival, migration, differentiation, neurite outgrowth, myelination, synaptic plasticity and regeneration after injury. Our previous study has demonstrated that overexpressing L1 enhances cell survival and proliferation of mouse embryonic stem cells (ESCs) through promoting the expression of FUT9 and ST3Gal4, which upregulates cell surface sialylation and fucosylation. In the present study, we examined whether sialylation and fucosylation are involved in ESC differentiation through L1 signaling. RNA interference analysis showed that L1 enhanced differentiation of ESCs into neurons through the upregulation of FUT9 and ST3Gal4. Furthermore, blocking the phospholipase Cγ (PLCγ) signaling pathway with either a specific PLCγ inhibitor or knockdown PLCγ reduced the expression levels of both FUT9 and ST3Gal4 mRNAs and inhibited L1-mediated neuronal differentiation. These results demonstrate that L1 promotes neuronal differentiation from ESCs through the L1-mediated enhancement of FUT9 and ST3Gal4 expression.
Keywords:L1  Cell differentiation  ESC (embryonic stem cell)  Glycosylation  PLCγ
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