Increased myelinating capacity of embryonic stem cell derived oligodendrocyte precursors after treatment by interleukin-6/soluble interleukin-6 receptor fusion protein.
Neurosphere cells (NSc) derived from embryonic stem cells have characteristics of neural stem cells and can differentiate into oligodendrocyte precursors. Culture of NSc with IL6RIL6 chimera (soluble interleukin-6 receptor fused to interleukin-6) enhances their differentiation into oligodendrocytes with longer and more numerous branches and with peripheral accumulation of myelin basic protein (MBP) in myelin membranes indicating maturation. Gene expression profiling reveals that one of the proteins strongly induced by IL6RIL6 is a regulator of microtubule dynamics, stathmin-like 2 (SCG10/Stmn2), and gene silencing shows that Stmn2 plays an important role in the development of the mature oligodendrocyte morphology. IL6RIL6 acts as an effective stimulator of the myelinating function of ES cell-derived oligodendrocyte precursors, as observed upon transplantation of the IL6RIL6- pretreated cells into brain slices of MBP-deficient shiverer mice.
Zhang
Pei-Lin
PL
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
Izrael
Michal
M
Ainbinder
Elena
E
Ben-Simchon
Levana
L
Chebath
Judith
J
Revel
Michel
M
D000818:Animals; D002135:Calcium-Binding Proteins; D018929:Cell Culture Techniques / Q000379:methods; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D009924:Organ Culture Techniques; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D050777:Stathmin; D033581:Stem Cell Transplantation / Q000379:methods; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002135:Calcium-Binding Proteins; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D019947:Receptors, Interleukin-6; D011993:Recombinant Fusion Proteins; D050777:Stathmin; C512849:Stmn2 protein, mouse