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J Cell Sci. 2018 Dec 17;131(24). pii: jcs219204. doi: 10.1242/jcs.219204.

Glycosphingolipid metabolism in cell fate specification.

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Institute of Protein Biochemistry, National Research Council, Via P. Castellino 111, Napoli, Italy
Institute of Protein Biochemistry, National Research Council, Via P. Castellino 111, Napoli, Italy.
Institute of Bioengineering, Laboratory of Lipid Cell Biology, École polytechnique fédérale de Lausanne (EPFL) CH-1015 Lausanne, Switzerland.


Glycosphingolipids (GSLs) are ubiquitous components of eukaryotic plasma membranes that consist of a ceramide backbone linked to a glycan moiety. Both the ceramide and the glycan parts of GSLs display structural variations that result in a remarkable repertoire of diverse compounds. This diversity of GSLs is exploited during embryogenesis, when different GSLs are produced at specific developmental stages and along several differentiation trajectories. Importantly, plasma membrane receptors interact with GSLs to modify their activities. Consequently, two otherwise identical cells can respond differently to the same stimulus owing to their different GSL composition. The metabolic reprograming of GSLs is in fact a necessary part of developmental programs, as its impairment results in developmental failure or tissue-specific defects. Moreover, single-cell variability is emerging as a fundamental player in development: GSL composition displays cell-to-cell variability in syngeneic cell populations owing to the regulatory gene expression circuits involved in microenvironment adaptation and in differentiation. Here, we discuss how GSLs are synthesized and classified and review the role of GSLs in the establishment and maintenance of cell identity. We further highlight the existence of the regulatory circuits that modify GSL pathways and speculate how GSL heterogeneity might contribute to developmental patterning.


Differentiation; Glycosphingolipid; Golgi complex

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Conflict of interest statement

Competing interestsThe authors declare no competing or financial interests.

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