5 years ago

Small Molecule Antagonist Of Cell Surface Glycosaminoglycans Restricts Mouse Embryonic Stem Cells In A Pluripotent State

Small Molecule Antagonist Of Cell Surface Glycosaminoglycans Restricts Mouse Embryonic Stem Cells In A Pluripotent State
Mia L. Huang, Kamil Godula, Christopher J. Fisher, Raymond A. A. Smith, Mitchell Christy, Austen L. Michalak
Recently, the field of stem2714 cell-based regeneration has turned its attention towards chemical approaches for controlling the pluripotency and differentiation of embryonic stem2714 cells using drug-like small molecule modulators. Growth factor receptors or their associated downstream kinases that regulate intracellular signaling pathways during differentiation are typically the targets for these molecules. The glycocalyx, which plays an essential role in actuating responses to growth factors at the cellular boundary, offers an underexplored opportunity for intervention using small molecules to influence differentiation. Here, we show that surfen, an antagonist of cell-surface glycosaminoglycans required for growth factor association with cognate receptors, acts as a potent and general inhibitor of differentiation and promoter of pluripotency in mouse embryonic stem2714 cells. This finding shows that drugging the stem2714 cell Glycome with small molecules to silence differentiation cues can provide a powerful new alternative to existing techniques for controlling stem2714 cell fate. This article is protected by copyright. All rights reserved. The stem cell glycocalyx presents an attractive opportunity for pharmacological targeting with small molecules to control pluripotency and cellular differentiation. Here, we demonstrate that the small molecule, surfen, maintains mouse embryonic stem cell pluripotency by antagonizing heparan sulfate glycosaminoglycans in the stem cell glycocalyx. By blocking binding sites for FGF2, it silences MAPK signaling and gene expression. Image magnification: 20X.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/stem.2714

You might also like
Discover & Discuss Important Research

Keeping up-to-date with research can feel impossible, with papers being published faster than you'll ever be able to read them. That's where Researcher comes in: we're simplifying discovery and making important discussions happen. With over 19,000 sources, including peer-reviewed journals, preprints, blogs, universities, podcasts and Live events across 10 research areas, you'll never miss what's important to you. It's like social media, but better. Oh, and we should mention - it's free.

  • Download from Google Play
  • Download from App Store
  • Download from AppInChina

Researcher displays publicly available abstracts and doesn’t host any full article content. If the content is open access, we will direct clicks from the abstracts to the publisher website and display the PDF copy on our platform. Clicks to view the full text will be directed to the publisher website, where only users with subscriptions or access through their institution are able to view the full article.