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Synthetic Glycopolymers for Highly Efficient Differentiation of Embryonic Stem Cells into Neurons: Lipo- or Not?
journal contribution
posted on 2017-03-13, 00:00 authored by Qi Liu, Zhonglin Lyu, You Yu, Zhen-Ao Zhao, Shijun Hu, Lin Yuan, Gaojian Chen, Hong ChenTo
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.
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Keywords
differentiationcell membrane receptorsSynthetic Glycopolymersphospholipid groupscell surface glycanfibroblast growth factor 2mouse ESCsbind FGF 2pSGF-treated cellsday 14.neurodegenerative diseaseslipo-pSGF-treated cellslipid-anchored GAG-mimicking glycopolymersEmbryonic Stem Cells1 hERKEfficient Differentiationneural-specific maker β3- tubulin
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