Essential roles of sphingosine-1-phosphate and platelet-derived growth factor in the maintenance of human embryonic stem cells.
Human embryonic stem cells (hESCs) have great potential for use in research and regenerative medicine, but very little is known about the factors that maintain these cells in the pluripotent state. We investigated the role of three major mitogenic agents present in serum--sphingosine-1-phosphate (S1P), lysophosphatidic acid (LPA), and platelet-derived growth factor (PDGF)--in maintaining hESCs. We show here that although LPA does not affect hESC growth or differentiation, coincubation of S1P and PDGF in a serum-free culture medium successfully maintains hESCs in an undifferentiated state. Our studies indicate that signaling pathways activated by tyrosine kinase receptors act synergistically with those downstream from lysophospholipid receptors to maintain hESCs in the undifferentiated state. This study is the first demonstration of a role for lysophospholipid receptor signaling in the maintenance of stem cell pluri-potentiality.
Pébay
Alice
A
Monash Institute of Medical Research, Laboratory of Embryonic Stem Cell Biology, Australian Stem Cell Centre, STRIP Monash University, Clayton VIC 3800, Australia. alice.pebay@med.monash.edu.au
Wong
Raymond C B
RC
Pitson
Stuart M
SM
Wolvetang
Ernst J
EJ
Peh
Gary S-L
GS
Filipczyk
Adam
A
Koh
Karen L L
KL
Tellis
Irene
I
Nguyen
Linh T V
LT
Pera
Martin F
MF
D018929:Cell Culture Techniques; D002478:Cells, Cultured; D033041:Embryo Research; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology / Q000502:physiology*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000187:drug effects / Q000235:genetics; D049368:Receptors, Lysophosphatidic Acid / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology*
D008246:Lysophospholipids; D010982:Platelet-Derived Growth Factor; D049368:Receptors, Lysophosphatidic Acid; C060506:sphingosine 1-phosphate; D020797:Receptor, Platelet-Derived Growth Factor beta; D013110:Sphingosine