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Enhancement of Oligodendrocyte Differentiation from Murine Embryonic Stem Cells by an Activator of gp130 Signaling

Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel

Key Words. Embryonic stem cells • Glial differentiation • gp130 • IL-6R/IL-6 fusion protein • In vitro differentiation • Oligodendrocytes

Michel Revel, M.D., Ph.D., Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, 76100, Israel. Telephone: 972-50-419763; Fax: 972-89-346106; e-mail: michel.revel{at}weizmann.ac.il

Embryonic stem (ES) cells derived from the inner cell mass of blastocyst-stage embryos are a potential large scale source of oligodendrocytes and of their progenitors for transplantation into the central nervous system for the repair of demyelinating lesions. We found previously that interleukin-6 (IL-6) fused to its soluble receptor (IL-6R), a potent activator of the gp130 receptor, induces myelin gene expression in Schwann cells of embryonic dorsal root ganglia. Like leukemia inhibitory factor, IL-6R/IL-6 inhibits the differentiation of murine ES cells into embryoid bodies. In the present study, we show that this recombinant cytokine may be efficiently used to stimulate the differentiation of oligodendrocytes if added to ES cell-derived neural precursors. IL-6R/IL-6 leads to an increase in early chondroitin sulfate proteoglycan positive and late O4 positive progenitors and to a stimulation of maturation into O1 and myelin basic protein expressing oligodendrocytes. Expression of the genes for transcription factor genes Olig-1 and Sox10, which appear early in the oligodendrocyte lineage, was stimulated by IL-6R/IL-6 addition. We conclude that this cytokine can significantly enhance the derivation of oligodendrocytes from ES cells.

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