Differential roles of astrocyte and microglia in supporting oligodendrocyte development and myelination in vitro

Abstract

Oligodendrocyte (OL) development relies on many extracellular cues, most of which are secreted cytokines from neighboring neural cells. Although it is generally accepted that both astrocytes and microglia are beneficial for OL development, there is a lack of understanding regarding whether astrocytes and microglia play similar or distinct roles. The current study examined the effects of astrocytes and microglia on OL developmental phenotypes including cell survival, proliferation, differentiation, and myelination in vitro. Our data reveal that, although both astrocytes- and microglia-conditioned medium (ACDM and MCDM, respectively) protect OL progenitor cells (OPCs) against growth factor withdrawal-induced apoptosis, ACDM is significantly more effective than MCDM in supporting long-term OL survival. In contrast, MCDM preferentially promotes OL differentiation and myelination. These differential effects of ACDM and MCDM on OL development are highlighted by distinct pattern of cytokine/growth factors in the conditioned medium, which correlates with differentially activated intracellular signaling pathways in OPCs upon exposure to the conditioned medium.

Heterogeneous astrocytes: Active players in CNS

“…Increasing evidences indicated that astrocytes play critical roles in OPCs and OLs survival, maturity and myelination through the intercellular crosstalk (Fischer et al 2014;Pang et al 2013;Stoffels et al 2015;Su et al 2011). The heterogeneous phenotypes of astrocytes are shown to relevantly affect the myelination capacity.…”

Accelerated generation of oligodendrocyte progenitor cells from human induced pluripotent stem cells by forced expression of Sox10 and Olig2

“…At day 15, we observed OPC-like cells with a bipolar morphology (Figure 2A-D) and the iOPCs could proliferate in response to PDGF-AB and bFGF (Pang et al, 2013) from groups with viral infection. Cells from the four groups were stained for PDGFRα.…”

“…The results showed that the proportion of PDGFRα + cells from Sox10+Olig2 group was more than that of single factor groups, which was further higher than that of negative control group ( Figure 2E-H, M). To investigate the differential capacity of iOPCs, cells were exposed to differential condition containing T3, NT3, IGF-1 (known to be beneficial for oligodendrocyte differentiation or survival) (Douvaras and Fossati, 2015;Najm et al, 2013;Pang et al, 2013). Cells were stained with O4 antibodies (Douvaras and Fossati, 2015;Pang et al, 2013;Yang et al, 2013) every other week to test whether induced oligodendrocytes (iOLs) had appeared.…”

“…To investigate the differential capacity of iOPCs, cells were exposed to differential condition containing T3, NT3, IGF-1 (known to be beneficial for oligodendrocyte differentiation or survival) (Douvaras and Fossati, 2015;Najm et al, 2013;Pang et al, 2013). Cells were stained with O4 antibodies (Douvaras and Fossati, 2015;Pang et al, 2013;Yang et al, 2013) every other week to test whether induced oligodendrocytes (iOLs) had appeared. At the fourth week of differentiation, around 42% of cells were O4-positive in Sox10+Olig2 group, higher than that of single factor groups and the negative group ( Figure 2I-L, N).…”

The role of oligodendrocytes and their progenitors on neural interface technology: A novel perspective on tissue regeneration and repair

“…However, galectin-1 attenuates the loss of myelin and neurodegeneration in animal models for MS [107]. Interestingly, non-reactive microglia and astrocytes influence NG2 glia differently [108]. Astrocyte-derived medium, which consists of increased PDGF-AA, FGF2, CNTF, and growth hormones, promotes proliferation of NG2 glia while microglia-derived medium, consisting more of IGF-1, CX3CL1, IL-2, and IL-5, promotes the differentiation of NG2 glia, indicating different fundamental roles in regulating the fate of oligodendroglia [100].…”