title: Synthetic Glycopolymers for Highly Efficient Differentiation of Embryonic Stem Cells into Neurons: Lipo- or Not?
abstract: To realize the potential application of embryonic stem cells (ESCs) for the treatment of neurodegenerative diseases, it is a prerequisite to develop an effective strategy for the neural differentiation of ESCs so as to obtain adequate amount of neurons. Considering the efficacy of glycosaminoglycans (GAG) and their disadvantages (e.g., structure heterogeneity and impurity), GAG-mimicking glycopolymers (designed polymers containing functional units similar to natural GAG) with or without phospholipid groups were synthesized in the present work and their ability to promote neural differentiation of mouse ESCs (mESCs) was investigated. It was found that the lipid-anchored GAG-mimicking glycopolymers (lipo-pSGF) retained on the membrane of mESCs rather than being internalized by cells after 1 h of incubation. Besides, lipo-pSGF showed better activity in promoting neural differentiation. The expression of the neural-specific maker β3-tubulin in lipo-pSGF-treated cells was ∼3.8- and ∼1.9-fold higher compared to natural heparin- and pSGF-treated cells at day 14. The likely mechanism involved in lipo-pSGF-mediated neural differentiation was further investigated by analyzing its effect on fibroblast growth factor 2 (FGF2)-mediated extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway which is important for neural differentiation of ESCs. Lipo-pSGF was found to efficiently bind FGF2 and enhance the phosphorylation of ERK1/2, thus promoting neural differentiation. These findings demonstrated that engineering of cell surface glycan using our synthetic lipo-glycopolymer is a highly efficient approach for neural differentiation of ESCs and this strategy can be applied for the regulation of other cellular activities mediated by cell membrane receptors.
authors.affiliation: State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University , 199 Ren'ai Road, Suzhou 215123, P.R. China.|Center for Soft Condensed Matter Physics and Interdisciplinary Research, Soochow University , Suzhou 215006, P.R. China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Liu
authors.affiliation: State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University , 199 Ren'ai Road, Suzhou 215123, P.R. China.
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Lyu
authors.affiliation: Institute for Cardiovascular Science and Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University , Suzhou 215000, P.R. China.
authors.forename: You
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Institute for Cardiovascular Science and Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University , Suzhou 215000, P.R. China.
authors.forename: Zhen-Ao
authors.initials: ZA
authors.lastname: Zhao
authors.affiliation: Institute for Cardiovascular Science and Department of Cardiovascular Surgery of the First Affiliated Hospital, Soochow University , Suzhou 215000, P.R. China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Hu
authors.affiliation: State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University , 199 Ren'ai Road, Suzhou 215123, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.affiliation: State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University , 199 Ren'ai Road, Suzhou 215123, P.R. China.|Center for Soft Condensed Matter Physics and Interdisciplinary Research, Soochow University , Suzhou 215006, P.R. China.
authors.forename: Gaojian
authors.initials: G
authors.lastname: Chen
authors.affiliation: State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials, College of Chemistry, Chemical Engineering and Materials Science, Soochow University , 199 Ren'ai Road, Suzhou 215123, P.R. China.
authors.forename: Hong
authors.identifier: http://orcid.org/0000-0001-7799-4961
authors.initials: H
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D051379:Mice; D048052:Mitogen-Activated Protein Kinase 3; D000066450:Mouse Embryonic Stem Cells; D009474:Neurons
chemical_list: D048052:Mitogen-Activated Protein Kinase 3
keywords: cell surface engineering; glycosaminoglycan analogues; mouse embryonic stem cells; neural differentiation; synthetic glycopolymers