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

Kouko Tatsumi,Yuki Terada,Akio Wanaka,Takeaki Shinjo,Tatsuhide Tanaka,Kazuki Nakahara,Shoko Morita-Takemura,Hiroaki Okuda,Miwako Yamasaki,Yoshie Kawabe,Ayami Isonishi

doi:10.3389/fnana.2018.00008

Kouko Tatsumi, Yuki Terada + Show 9 more

Open Access

https://doi.org/10.3389/fnana.2018.00008

Copy DOI

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.

Highlights

The transcription factor Olig2 plays an essential role in the differentiation of oligodendrocytes and motor neurons in the embryonic spinal cord (Takebayashi et al, 2002; Zhou and Anderson, 2002), and in oligodendrocyte maturation in the developing ventral forebrain (Parras et al, 2007; Petryniak et al, 2007)
The cell type with strong YFP fluorescence and bushy morphology were mature astrocytes (Tatsumi et al, 2016), and we confirmed that the bushy cells were positive for mature astrocyte markers in various brain regions, such as SOX9, S100 calcium-binding protein B (S100β) (Figures 1C1–C3, D1–D3, Figure S1) in the cerebral cortex, rabbit anti-3-phosphoglycerate dehydrogenase (3-PGDH) (Figures 1E1–E3, Figure S1) in the facial nucleus (7N), glutamine synthetase (GS) (Figures 1F1–F3, Figure S1) in the subthalamic nucleus
The subcellular localization patterns varied among the mature markers; transcription factor SOX9 was found in the nucleus (Figure S1D), while the enzyme GS was primarily present in the cytoplasm, but was found little in the distal processes (Figure S1B)

Summary

Introduction

The transcription factor Olig plays an essential role in the differentiation of oligodendrocytes and motor neurons in the embryonic spinal cord (Takebayashi et al, 2002; Zhou and Anderson, 2002), and in oligodendrocyte maturation in the developing ventral forebrain (Parras et al, 2007; Petryniak et al, 2007). A number of genetic fate-mapping studies using Olig2CreER mice have demonstrated that Olig2-positive cells (Olig cells) generate oligodendrocytes, astrocytes and neurons in the developing brain, and their differentiation properties vary in a brain regionspecific manner (Miyoshi et al, 2007; Ono et al, 2008). These detailed studies support the concept that Olig cells form heterogeneous progenitor pools in the developing forebrain (Ono et al, 2008). In injured or pathological states of the adult brain, Olig cells generate OPCs/NG2 glia, mature oligodendrocytes and a portion of reactive astrocytes, but, again, not neurons

Methods

Results

Conclusion