title: SOX17 is expressed in regenerating oligodendrocytes in experimental models of demyelination and in multiple sclerosis.
abstract: We have previously demonstrated that Sox17 expression is prominent at developmental stages corresponding to oligodendrocyte progenitor cell (OPC) cycle exit and onset of differentiation, and that Sox17 promotes initiation of OPC differentiation. In this study, we examined Sox17 expression and regulation under pathological conditions, particularly in two animal models of demyelination/remyelination and in post-mortem multiple sclerosis (MS) brain lesions. We found that the number of Sox17 expressing cells was significantly increased in lysolecithin (LPC)-induced lesions of the mouse spinal cord between 7 and 30 days post-injection, as compared with controls. Sox17 immunoreactivity was predominantly detected in Olig2(+) and CC1(+) oligodendrocytes and rarely in NG2(+) OPCs. The highest density of Sox17(+) oligodendrocytes was observed at 2 weeks after LPC injection, coinciding with OPC differentiation. Consistent with these findings, in cuprizone-treated mice, Sox17 expression was highest in newly generated and in maturing CC1(+) oligodendrocytes, but low in NG2(+) OPCs during the demyelination and remyelination phases. In MS tissue, Sox17 was primarily detected in actively demyelinating lesions and periplaque white matter. Sox17 immunoreactivity was co-localized with NOGO-A+ post-mitotic oligodendrocytes both in active MS lesions and periplaque white matter. Taken together, our data: (i) demonstrate that Sox17 expression is highest in newly generated oligodendrocytes under pathological conditions and could be used as a marker of oligodendrocyte regeneration, and (ii) are suggestive of Sox17 playing a critical role in oligodendrocyte differentiation and lesion repair.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U.975, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, Paris, France.
authors.forename: N M
authors.initials: NM
authors.lastname: Moll
authors.forename: E
authors.initials: E
authors.lastname: Hong
authors.forename: M
authors.initials: M
authors.lastname: Fauveau
authors.forename: M
authors.initials: M
authors.lastname: Naruse
authors.forename: C
authors.initials: C
authors.lastname: Kerninon
authors.forename: V
authors.initials: V
authors.lastname: Tepavcevic
authors.forename: A
authors.initials: A
authors.lastname: Klopstein
authors.forename: D
authors.initials: D
authors.lastname: Seilhean
authors.forename: L-J
authors.initials: LJ
authors.lastname: Chew
authors.forename: V
authors.initials: V
authors.lastname: Gallo
authors.forename: B
authors.initials: B
authors.lastname: Nait Oumesmar
mesh_terms: D000368:Aged; D000818:Animals; D000941:Antigens / Q000378:metabolism; D000071183:Autophagy-Related Proteins; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D001921:Brain / Q000473:pathology*; D001973:Bromodeoxyuridine / Q000378:metabolism; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity; D009103:Multiple Sclerosis / Q000473:pathology*; D004676:Myelin Basic Protein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D055760:SOXF Transcription Factors / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D000941:Antigens; D000071183:Autophagy-Related Proteins; D051792:Basic Helix-Loop-Helix Proteins; D001973:Bromodeoxyuridine; D003471:Cuprizone; D047908:Intracellular Signaling Peptides and Proteins; D017493:Leukocyte Common Antigens; D008070:Lipopolysaccharides; D008996:Monoamine Oxidase Inhibitors; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D011509:Proteoglycans; D055760:SOXF Transcription Factors; D000099216:Chondroitin Sulfate Proteoglycan 4; C405708:OLIG2 protein, human; C428743:Rb1cc1 protein, mouse; C109188:SOX17 protein, human
keywords: multiple sclerosis; oligodendrocyte differentiation; remyelination; transcription factors