title: Gap junctions modulate apoptosis and colony growth of human embryonic stem cells maintained in a serum-free system.
abstract: We investigated the gap junctional properties of human embryonic stem cells (hESC) cultivated in a serum-free system using sphingosine-1-phosphate and platelet-derived growth factor (S1P/PDGF). We compared this condition to hESC grown on Matrigel in mouse embryonic fibroblast conditioned medium (MEF-CM) or unconditioned medium (UM). We show that in all culture systems, hESC express connexins 43 and 45. hESC maintained in S1P/PDGF conditions and hESC grown in presence of MEF-CM are coupled through gap junctions while hESC maintained on Matrigel in UM do not exhibit gap junctional intercellular communication. In this latter condition, coupling was retrieved by addition of noggin, suggesting that BMP-like activity in UM inhibits gap junctional communication. Last, our data indicate that the closure of gap junctions by the decoupling agent alpha-glycyrrhetinic acid increases cell apoptosis and inhibits hESC colony growth. Altogether, these results suggest that gap junctions play an important role in hESC maintenance.
authors.affiliation: Monash Institute of Medical Research, Laboratory of Embryonic Stem Cell Biology, Australian Stem Cell Centre, Building 75, STRIP Monash University, Wellington Road, Clayton, Vic. 3800, Australia.
authors.forename: Raymond C B
authors.initials: RC
authors.lastname: Wong
authors.forename: Mirella
authors.initials: M
authors.lastname: Dottori
authors.forename: Karen L L
authors.initials: KL
authors.lastname: Koh
authors.forename: Linh T V
authors.initials: LT
authors.lastname: Nguyen
authors.forename: Martin F
authors.initials: MF
authors.lastname: Pera
authors.forename: Alice
authors.initials: A
authors.lastname: Pébay
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects / Q000502:physiology*; D018929:Cell Culture Techniques; D003094:Collagen / Q000494:pharmacology; D018031:Connexin 43 / Q000378:metabolism; D017630:Connexins / Q000378:metabolism; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D004622:Embryo, Mammalian / Q000166:cytology; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D006034:Glycyrrhetinic Acid / Q000494:pharmacology; D006801:Humans; D007797:Laminin / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011509:Proteoglycans / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D000099176:Noggin Protein
chemical_list: D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D003094:Collagen; D018031:Connexin 43; D017630:Connexins; D017077:Culture Media, Conditioned; D004338:Drug Combinations; D006034:Glycyrrhetinic Acid; D007797:Laminin; D008246:Lysophospholipids; D010982:Platelet-Derived Growth Factor; D011509:Proteoglycans; D013110:Sphingosine; D000099176:Noggin Protein; C082920:connexin 45; C059485:matrigel; C060506:sphingosine 1-phosphate