There is more to a lipid than just being a fat

Sphingolipid-Guided differentiation of oligodendroglial lineage from embryonic stem cells

Erhard Bieberich

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1601-1611
Number of pages11
JournalNeurochemical Research
Volume36
Issue number9
DOIs
StatePublished - Sep 1 2011

Fingerprint

Sphingolipids
Embryonic Stem Cells
Stem cells
Ceramides
Fats
Pluripotent Stem Cells
Lipids
Glycosphingolipids
Stem Cell Transplantation
Cell Differentiation
Lysosphingolipid Receptors
Apoptosis
Oligodendroglia
Prodrugs
Embryonic Development
Stem Cells
Transplantation
Brain
Research
Fingolimod Hydrochloride

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Biochemistry

Cite this

There is more to a lipid than just being a fat : Sphingolipid-Guided differentiation of oligodendroglial lineage from embryonic stem cells. / Bieberich, Erhard.

In: Neurochemical Research, Vol. 36, No. 9, 01.09.2011, p. 1601-1611.

Research output: Contribution to journalArticle

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