The role of nuclear receptors in the differentiation of oligodendrocyte precursor cells derived from fetal and adult neural stem cells

Abstract

Oligodendrocyte precursor cells (OPCs) differentiation from multipotent neural stem cells (NSCs) into mature oligodendrocytes is driven by thyroid hormone and mediated by thyroid hormone receptors (TRs). We show that several nuclear receptors display strong changes in expression levels between fetal and adult NSCs, with an overexpression of TRβ and a lower expression of RXRγ in adult. Such changes may determine the reduced capacity of adult OPCs to differentiate as supported by reduced yield of maturation and compromised mRNA expression of key genes. RXRγ may be the determinant of these differences, on the evidence of reduced number of mature oligodendrocytes and increased number of proliferating OPCs in RXRγ−/− cultures. Such data also points to RXRγ as an important regulator of the cell cycle exit, as proved by the dysregulation of T3-induced cell cycle exit-related genes.Our data highlight the biological differences between fetal and adult OPCs and demonstrate the essential role of RXRγ in the T3-mediated OPCs maturation process. Keywords: Oligodendrocyte precursor cells, Thyroid hormone, Retinoic X receptor gamma, Myelination, Remyelination