Olig2-Lineage Astrocytes: A Distinct Subtype of Astrocytes That Differs from GFAP Astrocytes

Abstract

Astrocytes are the most abundant glia cell type in the central nervous system (CNS), and are known to constitute heterogeneous populations that differ in their morphology, gene expression and function. Although glial fibrillary acidic protein (GFAP) is the cardinal cytological marker of CNS astrocytes, GFAP-negative astrocytes can easily be found in the adult CNS. Astrocytes are also allocated to spatially distinct regional domains during development. This regional heterogeneity suggests that they help to coordinate post-natal neural circuit formation and thereby to regulate eventual neuronal activity. Here, during lineage-tracing studies of cells expressing Olig2 using Olig2CreER; Rosa-CAG-LSL-eNpHR3.0-EYFP transgenic mice, we found Olig2-lineage mature astrocytes in the adult forebrain. Long-term administration of tamoxifen resulted in sufficient recombinant induction, and Olig2-lineage cells were found to be preferentially clustered in some adult brain nuclei. We then made distribution map of Olig2-lineage astrocytes in the adult mouse brain, and further compared the map with the distribution of GFAP-positive astrocytes visualized in GFAPCre; Rosa-CAG-LSL-eNpHR3.0-EYFP mice. Brain regions rich in Olig2-lineage astrocytes (e.g., basal forebrain, thalamic nuclei, and deep cerebellar nuclei) tended to lack GFAP-positive astrocytes, and vice versa. Even within a single brain nucleus, Olig2-lineage astrocytes and GFAP astrocytes frequently occupied mutually exclusive territories. These findings strongly suggest that there is a subpopulation of astrocytes (Olig2-lineage astrocytes) in the adult brain, and that it differs from GFAP-positive astrocytes in its distribution pattern and perhaps also in its function. Interestingly, the brain nuclei rich in Olig2-lineage astrocytes strongly expressed GABA-transporter 3 in astrocytes and vesicular GABA transporter in neurons, suggesting that Olig2-lineage astrocytes are involved in inhibitory neuronal transmission.

Developmental Maturation of the Cerebellar White Matter—an Instructive Environment for Cerebellar Inhibitory Interneurons

“…On the other hand, it is well established that cerebellar gray matter regions that are populated by distinct types of inhibitory interneurons are also characterized by strikingly different types of astroglia, thus as Bergman glia in the ML, and velate and protoplasmic astrocytes in the IGL (see [35,36] and [37] for detailed discussion). The yet distinct character of astrocytes in the DCN is again supported by our finding that their hallmark characteristic, i.e., the lack of GFAP expression [38], may be observed throughout their development.…”

Peptide‐modified, hyaluronic acid‐based hydrogels as a 3D culture platform for neural stem/progenitor cell engineering

“…3). While immunofluorescence staining revealed the presence of a few S100β + cells in both 2D and 3D cells in all conditions, overall low levels of S100β mRNA expression, which is often present even on fibrous astrocytes derived from olig2 + progenitors, in 3D culture provides evidence that the OLIG2 + cells observed at days 42 and 70 in 3D, differentiation culture are likely OPCs (Fig. A, B).…”

“…This shift from cytoplasmic to nuclear localization of OLIG2 protein indicates functional differentiation away from glial fibrillary acidic protein (GFAP)-positive astrocytes and toward progenitors of either oligodendrocytes, motor neurons, or fibrous astrocytes. 58,[76][77][78] Oligodendrocytelineage differentiation was characterized at days 42 (stem cell maintenance medium) and 70 (differentiation medium) using immunofluorescence staining for platelet-derived growth factor-α (PDGFR-α, OPCs), O4 (pre-oligodendrocytes), and 2 0 ,3 0 -cyclic-nucleotide 3 0 -phosphodiesterase (CNPase, pre-oligodendrocytes, and mature oligodendrocytes). 67,79,80 (Fig.…”

“…Implantation of HA hydrogels into the brain or spinal cord after injury can reduce the local inflammatory response and glial scar deposition . Furthermore, previous reports found that in vitro culture or ex vivo transplantation of NS/PCs within HA hydrogels with mechanical moduli mimicking healthy brain selectively increased differentiation of NS/PCs toward neurons or oligodendrocytes while decreasing astrocyte differentiation into reactive astrocytes …”

“…30,52 Furthermore, previous reports found that in vitro culture or ex vivo transplantation of NS/PCs within HA hydrogels with mechanical moduli mimicking healthy brain selectively increased differentiation of NS/PCs toward neurons or oligodendrocytes while decreasing astrocyte differentiation into reactive astrocytes. [53][54][55][56][57][58] In the present studies, we evaluated the effects of combinatorial presentation of laminin-derived adhesion peptides on survival, proliferation and differentiation of human NS/PCs in 3D culture. Laminins are key mediators of NS/PC progression to mature, myelinating oligodendrocytes.…”