Astrocytes regulate the expression of Sp1R3 on oligodendrocyte progenitor cells through Cx47 and promote their proliferation

Many degenerative diseases of the central nervous system are associated with demyelination. Oligodendrocyte progenitor cells (OPCs) are potential stem cells that can differentiate into various cell types, including oligodendrocytes (OLs). Promoting the proliferation and differentiation of OPCs into mature OLs that can myelinate axons is the key to stimulate remyelination. Here, we report that astrocytes (ASTs) increase the number of sphingosine-1-phosphate receptors 3 (S1pR3) on OPCs and promote OPCs proliferation through a direct contact via connexin 47 (Cx47). Our results demonstrate that ASTs can regulate the proliferation of OPCs through Cx47-mediated induction of S1pR3 expression on OPCs. Cx47/S1pR3 remarkably increases the number of OPCs and promotes cell transition from the G1 to the S phase. Furthermore, inhibiting either Cx47 or S1pR3 decreases OPC proliferation. In summary, ASTs regulate the expression of S1pR3 in OPCs via Cx47, which could be a valuable approach for promoting OPC proliferation. This strategy may therefore represent a potential treatment for neurological diseases caused by OLs death and demyelination.