Olig2+/NG2+/BLBP+ astrocyte progenitors: a novel component of the neurovascular unit in the developing mouse hippocampus

• Published in: Frontiers in cellular neuroscience Vol. 18; p. 1464402
• Main Authors: Omura, Shoichiro, Ogawa, Rina, Kawachi, Tomomi, Ogawa, Aya, Arai, Yuuki, Takayama, Natsumi, Masui, Aki, Kondo, Kumiko, Sugimoto, Hiroki, Shinohara, Hiroshi M, Takahashi, Tokiharu, Maeda, Hideyuki, Ohyama, Kyoji
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 17.10.2024
• Subjects: astrocyte progenitors; BLBP; Cellular Neuroscience; development; hippocampus; NG2; olig2; development; hippocampus; astrocyte progenitors; BLBP; NG2; olig2; neurovascular unit
• ISSN: 1662-5102; 1662-5102
• DOI: 10.3389/fncel.2024.1464402

Astrocytes are key components of the neurovascular unit. While we have recently identified Olig2+ astrocyte progenitors (ASPs) in the developing mouse dentate gyrus (DG), their molecular signature remains incompletely characterized. Here we demonstrate that Olig2+ ASPs predominantly express brain lipid-binding protein (BLBP), while only a small population of them expresses -GFP. These Olig2+/BLBP+ ASPs co-express the transcription factors Sox3, Sox9 and the proteoglycan NG2 but not Sox10, a marker for oligodendrocyte progenitors (OLPs). Olig2+ ASPs appear from embryonic day 18 (E18) onwards and decline at postnatal day 14 (P14). Consistent with the proliferation of both Olig2+ and NG2+ glial cells after brain injury, intrauterine intermittent hypoxia (IH) led to an increase in Olig2+/NG2+/BLBP+ ASPs in the postnatal DG. IH also promoted both angiogenesis and vascular coupling of Olig2+/NG2+ ASPs. Our data suggest that IH-induced expression of HIF1a increases Olig2+/NG2+/BLBP+ ASPs in a cell non-autonomous manner. Our data also revealed increased vascular coupling of GFAP+ astrocytes following IH, while the number of GFAP+ astrocytes remains unchanged. Given that BLBP, Olig2 and NG2 are expressed in reactive astrocytes, our findings suggest that Olig2+/NG2+/BLBP+ ASPs represent a subtype of reactive astrocyte progenitors. Furthermore, the enhanced vascular coupling of Olig2+/NG2+/BLBP+ ASPs appears to be an adaptive response to hypoxic brain injury. This study provides new insights into the molecular characteristics of Olig2+/NG2+/BLBP+ ASPs and their potential role in the brain's response to hypoxic injury, contributing to our understanding of neurovascular unit dynamics in both development and pathological conditions.