Alternatively Polarized Macrophages Regulate the Growth and Differentiation of Ependymal Stem Cells through the SIRT2 Pathway

ABSTRACT

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.