Mediation of apoptosis and proliferation of human embryonic stem cells by sphingosine-1-phosphate.

Human embryonic stem (hES) cells replicate by the process of self-renewal while maintaining their pluripotency. This process may be regulated by several different pathways and is poorly understood. In this study, sphingosine-1-phosphate (S1P) receptors were localized on hES cells of several cell lines (Shef 1-6), and their presence was verified by RT (reverse transcriptase)-PCR and western blotting. Dual staining with the stem cell marker Tra-1-60 revealed the presence of S1P receptors on pluripotential cells. Medium supplemented with 20 microM S1P significantly reduced the level of apoptosis in cultures of each of the Shef lines. S1P treatment was also found to statistically increase the level of proliferation in cell cultures. All Shef lines responded to S1P treatment in a similar manner; however, minor differences between cell lines were apparent. S1P directs cell fate decisions of many cell types. Here we demonstrate a role for S1P in hES cell survival by reducing apoptosis and increasing proliferation.