Olig1 is expressed in human oligodendrocytes during maturation and regeneration

Abstract

Myelin repair is inhibited in multiple sclerosis (MS), ultimately leading to axonal damage and disability. We aimed to understand the transcriptional mechanisms of regeneration in primary human oligodendrocyte cultures isolated from white matter of medically intractable epilepsy patients. Cultures at isolation contained 84% mature oligodendrocytes and 16% oligodendrocyte progenitor cells (OPC). The two populations showed a protracted regeneration of membranes expressing myelin proteins after 2-3 weeks in culture, and were kept long-term to study membranes maintenance. We profiled by quantitative PCR (qPCR) the sequential mRNA expression of transcription factors Olig1, Olig2, Nkx2.2, Sox10, PPARδ, PPARγ, cyclic nucleotide phosphodiesterase (CNP), myelin basic protein (MBP), myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (MOG). In summary, Olig1 was not expressed in freshly isolated oligodendrocytes, but was expressed from the beginning of process extension until membranes maintenance. In contrast, Olig2 expression was restricted to isolation and during membranes production. We show for the first time PPARδ expression and absence of PPARγ in human oligodendrocytes. Nkx2.2, Sox10, PPARδ, CNP, MBP and MOG messengers were expressed at any time, while MAG messenger was expressed at mature stage only. Myelin proteins CNP, MBP, MAG, and MOG were confirmed by immunocytochemistry. Our findings point to different roles of Olig1 and Olig2 in regeneration of cultured adult human oligodendrocytes. Noticeably, the transcriptional profiles found in cultured neonatal rodent OPC are different. More studies are necessary to elucidate myelin repair in the adult human brain.

RETRACTED ARTICLE: Effect of catalpol on remyelination through experimental autoimmune encephalomyelitis acting to promote Olig1 and Olig2 expressions in mice

“…These cells proliferated but failed to mature, since Olig1 was poorly expressed in the PA-treatment group. Olig1 can promote the functions of Olig2 [65, 69], and it plays an essential role in the differentiation and remyelination of OLs by maintaining Olig2 expression [67, 70]. Olig1−/− mice were characterized by the normal recruitment of OPCs, but these OPCs failed to differentiate into mature OLs [65].…”

A selective thyroid hormone β receptor agonist enhances human and rodent oligodendrocyte differentiation

“…5). As previously reported in the literature, we found that T3 promoted human CNP + OL differentiation (Othman et al, 2011; Wilson et al, 2003). Treatment with GC-1 (20 nM) induced an increase (from 15 to 35%) in the number of CNP + human OLs similar to that of T3 treatment and significantly greater than that of PDGF withdrawal alone (15 to 19%, n = 3, P < 0.05, One-Way ANOVA).…”

Negative regulation of miRNA-9 on oligodendrocyte lineage gene 1 during hypoxic-ischemic brain damage

“…A recent study confirmed that Olig1 was necessary for repair of the myelin sheath of transplanted neural progenitor cells in models of virus-induced demyelination[15]. Olig1 is expressed during the maturity and regeneration of human oligodendrocytes[1617]. Our pilot experiments verified that increased Olig1 gene expression contributed to myelin basic protein expression, indicating that the Olig1 gene played an important role in the repair of the myelin sheath.…”