Kim Sun Young, Kelland Eve E, Kim Ji Hong, Lund Brett T, Chang Xiao, Wang Kai, Weiner Leslie P
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089, USA.
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Biochem Biophys Rep. 2016 Dec 31;9:166-172. doi: 10.1016/j.bbrep.2016.12.004. eCollection 2017 Mar.
Retinoic acid (RA), a metabolite of vitamin A, has been found to influence regeneration in the adult central nervous system (CNS). There may be an effect of RA in the recovery/repair in multiple sclerosis (MS), an autoimmune and neurodegenerative disease of the CNS. We hypothesized that RA is a regulator of the further differentiation of oligodendrocyte precursor cells (OPCs) - cells key to the remyelination process in MS. We conducted studies utilizing RNA-sequencing in human embryonic stem cell (hESC)-derived neural stem cells (NSCs) and OPCs so as to understand the role of transcriptional regulators during transition from both ESCs to NSCs and NSCs to OPCs. We identified that expression of retinoic acid receptors β and γ ( and ) was significantly increased following the transition from NSCs to OPCs. We also demonstrated that long term culture of hESC-derived OPC with different isoforms of RA led to the significant up-regulation of two known transcriptional inhibitors of oligodendrocyte differentiation: following prolonged treatment with all-trans-RA, 9-cis RA and 13-cis RA; and following treatment with 13cisRA. These results suggest that long term exposure to certain RA isoforms may impact the continued differentiation of this population.
视黄酸（RA）是维生素A的一种代谢产物，已被发现可影响成体中枢神经系统（CNS）的再生。在多发性硬化症（MS）中，RA可能对恢复/修复过程产生影响，MS是一种中枢神经系统的自身免疫性和神经退行性疾病。我们推测RA是少突胶质前体细胞（OPC）进一步分化的调节因子，而OPC是MS髓鞘再生过程中的关键细胞。我们利用RNA测序技术对人胚胎干细胞（hESC）来源的神经干细胞（NSC）和OPC进行了研究，以了解转录调节因子在从胚胎干细胞向神经干细胞以及从神经干细胞向少突胶质前体细胞转变过程中的作用。我们发现，从神经干细胞向少突胶质前体细胞转变后，视黄酸受体β和γ（ 和 ）的表达显著增加。我们还证明，用不同异构体的视黄酸对hESC来源的少突胶质前体细胞进行长期培养，会导致两种已知的少突胶质细胞分化转录抑制剂显著上调：在用全反式视黄酸、9-顺式视黄酸和13-顺式视黄酸长期处理后上调；在用13-顺式视黄酸处理后上调。这些结果表明，长期暴露于某些视黄酸异构体可能会影响这群细胞的持续分化。
