Embryonic Stem Cell Engineering with a Glycomimetic FGF2/BMP4 Co-Receptor Drives Mesodermal Differentiation in a Three-Dimensional Culture

ACS Chemical Biology
Matthew R NaticchiaKamil Godula

Abstract

Cell surface glycans, such as heparan sulfate (HS), are increasingly identified as co-regulators of growth factor signaling in early embryonic development; therefore, chemical tailoring of HS activity within the cellular glycocalyx of stem cells offers an opportunity to control their differentiation. The growth factors FGF2 and BMP4 are involved in mediating the exit of murine embryonic stem cells (mESCs) from their pluripotent state and their differentiation toward mesodermal cell types, respectively. Here, we report a method for remodeling the glycocalyx of mutant Ext1-/- mESCs with defective biosynthesis of HS to drive their mesodermal differentiation in an embryoid body culture. Lipid-functionalized synthetic HS-mimetic glycopolymers with affinity for both FGF2 and BMP4 were introduced into the plasma membrane of Ext1-/- mESCs, where they acted as functional co-receptors of these growth factors and facilitated signal transduction through associated MAPK and Smad signaling pathways. We demonstrate that these materials can be employed to remodel Ext1-/- mESCs within three-dimensional embryoid body structures, providing enhanced association of BMP4 at the cell surface and driving mesodermal differentiation. As a more complete ...Continue Reading

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Citations

May 28, 2020·Proceedings of the National Academy of Sciences of the United States of America·Corleone S DelaverisCarolyn R Bertozzi
Feb 19, 2021·The Biochemical Journal·Meg CritcherMia L Huang
Mar 12, 2021·Chemical Communications : Chem Comm·Prashant JainRaghavendra Kikkeri
Dec 23, 2020·Trends in Biochemical Sciences·Benjamin P Kellman, Nathan E Lewis
Aug 3, 2021·Chemical Reviews·Lu SuGuosong Chen
Aug 5, 2021·Chemical Society Reviews·Yujun KimInjae Shin
Apr 21, 2020·Organic Letters·Saurabh AnandRaghavendra Kikkeri

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