5. EXTRACELLULAR MATRIX PROTEINS ARE NECESSARY FOR MOUSE EMBRYONIC STEM CELL DIFFERENTIATION AND MAY GUIDE STEM CELL FATE

Department: Bioengineering
Faculty Advisor(s): Adam J Engler

Primary Student
Name: Hermes Alexander Taylor-Weiner
Email: htaylorw@ucsd.edu
Phone: 858-246-1469
Grad Year: 2015

Abstract
While in vitro differentiation protocols often rely exclusively on soluble growth factors to direct mouse embryonic stem cell (mESC) fate, the ESC niche also contains fibrillar extracellular matrix (ECM) proteins, including fibronectin (FN) and laminin. Many soluble factors used in ESC differentiation are known to increase ECM expression, e.g. Activin A and FN, yet ECM's ability to direct ESC fate alone is not well understood and likely occurs at some points during development. To address this, we examined whether ECM proteins were necessary and/or sufficient to direct mESC differentiation into mesendodermal lineages. mESCs, grown for ten days as embryoid bodies under differentiating conditions in the absence of serum-form and cell-derived FN, maintained expression of the pluripotency marker, Nanog. The embryoid bodies also showed a spatiotemporal correlation between expression of FN and GATA4, a marker for differentiation, and an inverse correlation between FN and Nanog. When differentiated on gelatin, mESCs created a fibrillar ECM containing FN and laminin components-unlike conventional fibroblasts, which make FN only-while treatment with leukemia inhibitory factor inhibited fibrillar matrix production and maintained pluripotency. When endoderm growth factors Activin A and Wnt 3A are used in culture, cell-derived ECM composition changes, and this change is likely necessary but not sufficient to efficiently direct mESC differentiation. Together these data imply that FN is necessary for mESC differentiation and that the extracellular matrix may be an important director of stem cell fate.

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