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The Role of Sphingolipids in Modulating Pluripotency of Stem Cells

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Trends in Stem Cell Proliferation and Cancer Research

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Abstract

Sphingolipids are essential components in mammalian cell membranes and vital modulators of cellular signaling processes. Nine molecular types of glycosphingolipids (GSLs), along with sphingosine 1-phosphate (S1P), play crucial roles in stem cells. GSLs are generated via ceramide glycosylation, the first step of which is catalyzed by glucosylceramide synthase, followed by further alternative elaborations to globo-series, ganglio-series, and lacto-series GSLs. Certain globo-series GSLs, namely, Gb5 (stage-specific embryonic antigen 3) and MSGb5 (stage-specific embryonic antigen 4), are essential for maintaining pluripotency of embryonic stem cells , and a shift of globo-series to ganglio-series GSLs (GD3, GM3, GD2, GT3) is associated with differentiation of embryonic stem cells into neural stem cells. Stem properties of breast cancer stem cells (BCSCs) mainly rely on glucosylceramide synthase and globo-series GSLs (Gb3). GD2 is a newly adopted surface marker for identifying BCSCs, and is also an effective target for eradicating BCSCs. S1P, which is generated from sphingosine phosphorylation following ceramide hydrolysis, activates S1P receptors and regulates stem cell proliferation and differentiation. Fingolimod deactivates S1P receptors and induces brain tumor stem cell apoptosis and protects neural stem cells. Targeting selected enzymes controlling sphingolipid synthesis and degradation can maintain normal stem cells and eradicate cancer stem cells. GSLs and S1P modulate stem cells through cSrc/β-catenin and pathways, but the mechanistic implications require further studies for clarification.

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Acknowledgments

This work was supported by grants from the Mizutani Foundation for Glycoscience, the National Center for Research Resources (5P20RR016456-11), and the National Institute of General Medical Sciences (8 P20 GM103424-11) of the National Institutes of Health.

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  1. Department of Basic Pharmaceutical Sciences, University of Louisiana at Monroe, 700 University Avenue, Monroe, LA, 71209, USA

    Salman B. Hosain, Ronald A. Hill & Yong-Yu Liu

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  1. Salman B. Hosain
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  2. Ronald A. Hill
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  3. Yong-Yu Liu
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Correspondence to Yong-Yu Liu .

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  1. Instituto de Ciências Biológicas, Departamento de Bioquímica, Universidade Federal de Minas Gerais, Belo Horizonte, São Paulo, Brazil

    Rodrigo R. Resende

  2. Depto. Bioquímica, Universidade de São Paulo Inst. Química, São Paulo, São Paulo, Brazil

    Henning Ulrich

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Hosain, S.B., Hill, R.A., Liu, YY. (2013). The Role of Sphingolipids in Modulating Pluripotency of Stem Cells . In: Resende, R., Ulrich, H. (eds) Trends in Stem Cell Proliferation and Cancer Research. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6211-4_7

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