title: Signals from the surface modulate differentiation of human pluripotent stem cells through glycosaminoglycans and integrins.
abstract: The fate decisions of human pluripotent stem (hPS) cells are governed by soluble and insoluble signals from the microenvironment. Many hPS cell differentiation protocols use Matrigel, a complex and undefined substrate that engages multiple adhesion and signaling receptors. Using defined surfaces programmed to engage specific cell-surface ligands (i.e., glycosaminoglycans and integrins), the contribution of specific matrix signals can be dissected. For ectoderm and motor neuron differentiation, peptide-modified surfaces that can engage both glycosaminoglycans and integrins are effective. In contrast, surfaces that interact selectively with glycosaminoglycans are superior to Matrigel in promoting hPS cell differentiation to definitive endoderm and mesoderm. The modular surfaces were used to elucidate the signaling pathways underlying these differences. Matrigel promotes integrin signaling, which in turn inhibits mesendoderm differentiation. The data indicate that integrin-activating surfaces stimulate Akt signaling via integrin-linked kinase (ILK), which is antagonistic to endoderm differentiation. The ability to attribute cellular responses to specific interactions between the cell and the substrate offers new opportunities for revealing and controlling the pathways governing cell fate.
authors.affiliation: Departments of Biochemistry and.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Wrighton
authors.affiliation: Cell and Molecular Biology Program, University of Wisconsin-Madison, Madison, WI 53706; and.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Klim
authors.affiliation: Departments of Biochemistry and.
authors.forename: Brandon A
authors.initials: BA
authors.lastname: Hernandez
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53792.
authors.forename: Chad H
authors.initials: CH
authors.lastname: Koonce
authors.affiliation: Department of Medicine, University of Wisconsin-Madison, Madison, WI 53792.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Kamp
authors.affiliation: Departments of Biochemistry and Cell and Molecular Biology Program, University of Wisconsin-Madison, Madison, WI 53706; and Chemistry, kiessling@chem.wisc.edu.
authors.forename: Laura L
authors.initials: LL
authors.lastname: Kiessling
mesh_terms: D000595:Amino Acid Sequence; D002448:Cell Adhesion; D002454:Cell Differentiation; D005109:Extracellular Matrix / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000099200:Scaffold Protein ILK
chemical_list: D006025:Glycosaminoglycans; D016023:Integrins; D008565:Membrane Proteins; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK
keywords: biomaterials; cell signaling; human embryonic stem cells; integrin-linked kinase; proteoglycan