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Neurochemical Research

, Volume 36, Issue 9, pp 1601–1611 | Cite as

There is More to a Lipid than just Being a Fat: Sphingolipid-Guided Differentiation of Oligodendroglial Lineage from Embryonic Stem Cells

  • Erhard Bieberich
ORIGINAL PAPER

Abstract

Dr. Robert K. Yu’s research showed for the first time that the composition of glycosphingolipids is tightly regulated during embryo development. Studies in our group showed that the glycosphingolipid precursor ceramide is also critical for stem cell differentiation and apoptosis. Our new studies suggest that ceramide and its derivative, sphingosine-1-phosphate (S1P), act synergistically on embryonic stem (ES) cell differentiation. When using neural precursor cells (NPCs) derived from ES cells for transplantation, residual pluripotent stem (rPS) cells pose a significant risk of tumor formation after stem cell transplantation. We show here that rPS cells did not express the S1P receptor S1P1, which left them vulnerable to ceramide or ceramide analog (N-oleoyl serinol or S18)-induced apoptosis. In contrast, ES cell-derived NPCs expressed S1P1 and were protected in the presence of S1P or its pro-drug analog FTY720. Consistent with previous studies, FTY720-treated NPCs differentiated predominantly toward oligodendroglial lineage as tested by the expression of the oligodendrocyte precursor cell (OPC) markers Olig2 and O4. As the consequence, a combined administration of S18 and FTY720 to differentiating ES cells eliminated rPS cells and promoted oligodendroglial differentiation. In addition, we show that this combination promoted differentiation of ES cell-derived NPCs toward oligodendroglial lineage in vivo after transplantation into mouse brain.

Keywords

Ceramide Sphingosine-1-phosphate Embryonic stem cells Apoptosis Differentiation Oligodendrocyte precursors 

Abbreviations

aPKC

Atypical PKC

EB

Embryoid body

EBC

EB-derived cell

ES

Embryonic stem

iOPC

Induced oligodendrocyte precursor cell

MBP

Myelin basic protein

NP

Neural progenitor

NPC

Neural precursor cell

OPC

Oligodendrocyte precursor cell

PAR-4

Prostate apoptosis response 4

rPS

Residual pluripotent stem

S1P

Sphingosine-1-phoshate

S18

N-oleoyl serinol

Notes

Acknowledgments

This work was supported in part by the NIH grants R01AG034389 and R01NS046835 to EB. The author also acknowledges institutional support (under directorship of Dr. Lin Mei) at the Medical College of Georgia/Georgia Health Sciences University, Augusta, GA. We are thankful to the Imaging Core Facility (under directorship of Dr. Paul McNeil) for assistance with confocal microscopy.

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Program in Developmental Neurobiology, Institute of Molecular Medicine and Genetics, School of MedicineMedical College of Georgia/Georgia Health Sciences UniversityAugustaUSA

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