Morphogenetic Sphingolipids in Stem Cell Differentiation and Embryo Development

Abstract

The lipid composition in stem cells undergoes remarkable changes during neural differentiation. Growing evidence suggests that lipids regulate stem cell differentiation through three mechanisms: direct binding and regulation of lipid-specific receptors, regulation of non-lipid receptors by clustering with lipids in microdomains or rafts, and enrichment of specific lipids in compartments and vesicles. Lipid-driven compartmentalization is critical for vesicle trafficking, cell polarity and ultimately, embryo development. Sphingolipids such as ceramide are strictly compartmentalized to function in distinct differentiation programs. Research in our laboratory has focused on the function of ceramide-enriched compartments (CECs). Ceramide and its derivative, sphingosine-1-phosphate (S1P), are counteractive in stem cell apoptosis vs. survival, but they can act synergistically in neural progenitor cell differentiation. This review discusses studies on lipid-induced stem cell differentiation and embryo development with focus on sphingolipids as ``morphogenetic lipids'' and potential drug targets in regenerative medicine.