Targeting Glycosaminoglycan-mediated Growth Factor Signaling to Influence Stem Cell Specification

Targeting Glycosaminoglycan-mediated Growth Factor Signaling to Influence Stem Cell Specification

Powering Stem Cell Fate with Glycosaminoglycan Innovation

The growth factor (GF) signaling pathway determines the fate of stem cells. It activates key signaling pathways involved in gene regulation. Among them, glycosaminoglycans (GAGs) are important mediators of growth factor signaling. At CD BioGlyco, we have constructed a professional Glycan Display Platform, and to explore the effects of targeting GAG-mediated GF signaling on stem cells by probing GAG-mediated cell signaling in stem cell development.

  • Firstly, we provide reconfiguration of the glycocalyx. We manipulate the metabolic pathways responsible for glycan biosynthesis by covalently grafting GAGs to surface proteins or by passively inserting lipid-functionalized glycoconjugates into cell membranes. Here, we further explore their potentiation of nerve GF-mediated signaling.
  • Secondly, we construct a microarray platform to identify GAG candidate genes with GF specificity.
    • We prepare a key polymer intermediate primed for disaccharide-GAG coupling and terminated with an azide group. In this process, we use quantitative fluorescent labeling to facilitate subsequent detection.
    • A library of proteoglycan structures is obtained by reacting polymer intermediates with GAG couplers. Nuclear magnetic resonance (NMR) hydrogen spectroscopy is used to analyze the degree of incorporation of individual glycans and their binding to GFs. The degree of remodeling of different proteoglycans is assessed by fluorescence microscopy.
  • In addition, to change the effect of GAGs on GF activity, we offer modification of GAGs. We also provide a Western blot technique to analyze the effect of GAGs before and after modification.

Fig.1 Strategies to remodel cell surfaces with glycans. (CD BioGlyco)Fig.1 Targeting GAG-mediated GF signaling to influence stem cell specification-related service. (CD BioGlyco)

Publication

Technology: Cell surface engineering strategy

Journal: Journal of the American Chemical Society

IF: 15.0

Published: 2014

Results: The GF signaling pathway is a key determinant of stem cell fate. the interaction of GF with its receptor is usually mediated by heparan sulfate proteoglycans (hsgs). In this paper, the authors describe a cell surface engineering strategy that exploits the function of heat shock proteins to promote the differentiation of embryonic stem cells (ESCs). Authors have generated synthetic neo-proteoglycans (neoPGs) with an affinity for fibroblast growth factor 2 (FGF2) and introduced them into the plasma membrane of HS biosynthesis-deficient ESCs. Once there, neoPGs assumed the function of natural heat shock proteins, rescued FGF2-mediated kinase activity, and promoted neural differentiation. This strategy of glycocalyx remodeling is versatile and may apply to other types of differentiation.

Fig.2 Glycocalyx remodeling strategy for influencing stem cell specification. (Huang, et al., 2014)Fig.2 Glycocalyx remodeling strategy for influencing stem cell specification. (Huang, et al., 2014)

Applications

  • GAG-mediated modulation of GF signaling can be used to develop cell lineages and advance cell-based therapeutic research.
  • Targeting GAG-mediated GF signaling to affect stem cells can be used in research on cell-to-cell communication, development, and disease progression. It also provides a powerful means of directing activity and triggering desired cellular responses.

Advantages of Us

  • We provide custom De Novo Glycan Display services according to the client's requirements.
  • We have a professional R&D team and implement strict quality control processes to ensure that we provide high-quality services.
  • We not only provide relevant services suitable for small-scale experiments but also provide large-scale mass-production services.

CD BioGlyco focuses on research in the field of glycobiology and has constructed a professional glycan display platform to provide clients with comprehensive glycan display-related services. We are committed to relentlessly pursuing excellence in the quality of our services to help our clients maximize their research in the field of glycobiology. If you have inquiries or are interested in our services, please contact us without hesitation.

References

  1. Huang, M.L.; et al. Glycocalyx remodeling with proteoglycan mimetics promotes neural specification in embryonic stem cells. J. Am. Chem. Soc. 2014, 136: 10565-10568.
  2. Griffin, M.E.; et al. Glycan engineering for cell and developmental biology. Cell Chem Biol. 2016; 23(1): 108-121.
This service is for Research Use Only, not intended for any clinical use.

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