Ma Yonggang, Deng Ming, Zhao Xiao-Qi, Liu Min
Department of Orthopaedics, Renmin Hospital, Wuhan University, Wuhan 430060, China.
Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Wuhan 430071, China.
Exp Neurobiol. 2020 Apr 30;29(2):150-163. doi: 10.5607/en19078.
Ependymal stem cells (EpSCs) are dormant stem cells in the adult spinal cord that proliferate rapidly and migrate to the site of injury after spinal cord injury (SCI). Although they can differentiate into neurons under appropriate conditions in vitro, EpSCs mainly differentiate into astrocytes in vivo. Our previous study confirmed that alternatively polarized macrophages (M2) facilitate the differentiation of EpSCs towards neurons, but the detailed mechanism remains elusive. In the present study, we found that M2 conditioned medium could upregulate the expression of Sirtuin 2 (SIRT2) in EpSCs in vitro through the BDNF/TrkB-MEK/ERK signaling pathway. As an important deacetylase, SIRT2 deacetylated stable Ac-α-tubulin (Acetyl alpha Tubulin) in microtubules and thus promoted EpSC differentiation into neurons. The present study provides a theoretical basis and a new way to improve neural recovery, such as regulating the growth and differentiation of EpSCs by increasing the proportion of M2 cells in the local microenvironment or upregulating the expression of SIRT2 in EpSCs.
室管膜干细胞（EpSCs）是成年脊髓中的休眠干细胞，在脊髓损伤（SCI）后会迅速增殖并迁移到损伤部位。尽管它们在体外适当条件下可分化为神经元，但在体内EpSCs主要分化为星形胶质细胞。我们之前的研究证实，交替极化的巨噬细胞（M2）促进EpSCs向神经元的分化，但其详细机制仍不清楚。在本研究中，我们发现M2条件培养基可通过BDNF/TrkB-MEK/ERK信号通路在体外上调EpSCs中沉默调节蛋白2（SIRT2）的表达。作为一种重要的去乙酰化酶，SIRT2使微管中的稳定乙酰化α-微管蛋白（Acetyl alpha Tubulin）去乙酰化，从而促进EpSCs分化为神经元。本研究为改善神经恢复提供了理论依据和新途径，例如通过增加局部微环境中M2细胞的比例或上调EpSCs中SIRT2的表达来调节EpSCs的生长和分化。
