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-l-phosphate (SIP), 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 SIP 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 pluripotentiality. STEM C ELLS 2005;23:1541-1548.