title: Differentiation of cardiomyocytes from human embryonic stem cells is accompanied by changes in the extracellular matrix production of versican and hyaluronan.
abstract: Proteoglycans and hyaluronan play critical roles in heart development. In this study, human embryonic stem cells (hESC) were used as a model to quantify the synthesis of proteoglycans and hyaluronan in hESC in the early stages of differentiation, and after directed differentiation into cardiomyocytes. We demonstrated that both hESC and cardiomyocyte cultures synthesize an extracellular matrix (ECM) enriched in proteoglycans and hyaluronan. During cardiomyocyte differentiation, total proteoglycan and hyaluronan decreased and the proportion of proteoglycans bearing heparan sulfate chains was reduced. Versican, a chondroitin sulfate proteoglycan, accumulated in hESC and cardiomyocyte cultures. Furthermore, versican synthesized by hESC contained more N- and O-linked oligosaccharide than versican from cardiomyocytes. Transcripts for the versican variants, V0, V1, V2, and V3, increased in cardiomyocytes compared to hESC, with V1 most abundant. Hyaluronan in hESC had lower molecular weight than hyaluronan from cardiomyocyte cultures. These changes were accompanied by an increase in HAS-1 and HAS-2 mRNA in cardiomyocyte cultures, with HAS-2 most abundant. Interestingly, HAS-3 was absent from the cardiomyocyte cultures, but expressed by hESC. These results indicate that human cardiomyocyte differentiation is accompanied by specific changes in the expression and accumulation of ECM components and suggest a role for versican and hyaluronan in this process.
authors.affiliation: The Hope Heart Program, Benaroya Research Institute at Virginia Mason, Seattle, Washington, USA.
authors.forename: Christina K
authors.initials: CK
authors.lastname: Chan
authors.forename: Marsha W
authors.initials: MW
authors.lastname: Rolle
authors.forename: Susan
authors.initials: S
authors.lastname: Potter-Perigo
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Braun
authors.forename: Benjamin P
authors.initials: BP
authors.lastname: Van Biber
authors.forename: Michael A
authors.initials: MA
authors.lastname: Laflamme
authors.forename: Charles E
authors.initials: CE
authors.lastname: Murry
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Wight
mesh_terms: D002454:Cell Differentiation; D019070:Cell Lineage; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis* / Q000737:chemistry; D015394:Molecular Structure; D008970:Molecular Weight; D032383:Myocytes, Cardiac / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D053675:Versicans / Q000096:biosynthesis* / Q000737:chemistry
chemical_list: D053675:Versicans; D006820:Hyaluronic Acid