Journal of Cell Science & Therapy
Open Access

The extracellular matrix in stem cell commitment: Biphasic role of chondroitin sulfate in cardiac differentiation of embryonic stem cells through inhibition of Wnt/beta-catenin signaling

4^th World Congress on Cell Science & Stem Cell Research

June 24-26, 2014 Valencia Conference Centre, Valencia, Spain

Michael Kluppel

Scientific Tracks Abstracts: J Cell Sci Ther

Abstract :

T he glycosaminoglycan chondroitin sulfate is a critical component of proteoglycans on the cell surface and in the extracellular matrix. As such, chondroitin sulfate side chains and the sulfation balance of chondroitin play important roles in the control of signaling pathways, and have a functional importance in human disease. In contrast, very little is known about the roles of chondroitin sulfate molecules and sulfation patterns during mammalian development and cell lineage specification. Here, the author reports a novel biphasicrole of chondroitin sulfate in the specification of the cardiac cell lineage during embryonic stem cell differentiation through modulation of Wnt/beta-catenin signaling. Lineage marker analysis demonstrates that enzymatic elimination of endogenous chondroitin sulfates leads to defects specifically in cardiac differentiation. This is accompanied by a reduction in the number of beating cardiac foci. Mechanistically, it is shown that endogenous chondroitin sulfate controls cardiac differentiation in a temporal biphasic manner through inhibition of the Wnt/beta-catenin pathway, a known regulatory pathway for the cardiac lineage. Treatment with a specific exogenous chondroitin sulfate, CS-E, could mimic these biphasic effects on cardiac differentiation and Wnt/beta-catenin signaling. These results establish chondroitin sulfate and its sulfation balance as important regulators of cardiac cell lineage decisions through control of the Wnt/beta-catenin pathway. The work suggests that targeting the chondroitin biosynthesis and sulfation machinery is a novel promising avenue in regenerative strategies after heart injury

Biography :

Michael Kl�ppel received A Master?s degree from the University of Heidelberg, Germany, and his PhD from the University of Toronto, Canada. After Postdoctoral studies at The Hospital for Sick Children and Mount Sinai Hospital in Toronto, he currently holds an Assistant Professor position at the Feinberg School of Medicine of Northwestern University in Chicago. He has published more than 25 peer-reviewed papers inreputed journals, and serves as an editorial board member for several international journals