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Sphingosine Levels Key for Maintaining Stem Cell Fate

The function of the sphingosine‐1‐phosphate (S1P) signaling pathway in embryonic stem cells (ESCs) remains unclear; therefore, researchers led by Todd Evans (Weill Cornell Medicine, New York, New York, USA) recently employed a genetic approach to eliminate S1P from murine ESCs by deleting both sphingosine kinase orthologs. Reporting in STEM CELLS, Pandey et al. discovered that loss of both kinases inhibited ESC proliferation, with cells arresting at the G2/M checkpoint. However, as synthase expression reversed this phenotype, the accumulation of sphingosine caused the defect rather than the lack of S1P. The authors note that these data agree with previous results from early zebrafish embryos, suggesting a critical conserved role for limiting sphingosine levels in stem and progenitor cells.