Program in Developmental Biology, Baylor College of Medicine, Houston, TX, USA.
Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX, USA.
Nat Commun. 2021 Sep 1;12(1):5230. doi: 10.1038/s41467-021-25444-3.
The role of transcription factors during astrocyte development and their subsequent effects on neuronal development has been well studied. Less is known about astrocytes contributions towards circuits and behavior in the adult brain. Astrocytes play important roles in synaptic development and modulation, however their contributions towards neuronal sensory function and maintenance of neuronal circuit architecture remain unclear. Here, we show that loss of the transcription factor Sox9 results in both anatomical and functional changes in adult mouse olfactory bulb (OB) astrocytes, affecting sensory processing. Indeed, astrocyte-specific deletion of Sox9 in the OB results in decreased odor detection thresholds and discrimination and it is associated with aberrant neuronal sensory response maps. At functional level, loss of astrocytic Sox9 impairs the electrophysiological properties of mitral and tufted neurons. RNA-sequencing analysis reveals widespread changes in the gene expression profiles of OB astrocytes. In particular, we observe reduced GLT-1 expression and consequential alterations in glutamate transport. Our findings reveal that astrocytes are required for physiological sensory processing and we identify astrocytic Sox9 as an essential transcriptional regulator of mature astrocyte function in the mouse OB.
转录因子在星形胶质细胞发育及其对神经元发育的后续影响方面的作用已经得到了很好的研究。然而，人们对星形胶质细胞在成年大脑中的回路和行为中的贡献知之甚少。星形胶质细胞在突触发育和调节中发挥重要作用，但它们对神经元感觉功能和维持神经元回路结构的贡献仍不清楚。在这里，我们表明，转录因子 Sox9 的缺失会导致成年小鼠嗅球（OB）星形胶质细胞的解剖和功能变化，从而影响感觉处理。事实上，OB 中 Sox9 的星形胶质细胞特异性缺失会导致气味检测阈值和辨别能力降低，并且与异常的神经元感觉反应图谱相关。在功能水平上，丧失星形胶质细胞 Sox9 会损害僧帽细胞和丛状细胞的电生理特性。RNA 测序分析揭示了 OB 星形胶质细胞基因表达谱的广泛变化。特别是，我们观察到 GLT-1 表达减少，导致谷氨酸转运的改变。我们的研究结果表明，星形胶质细胞是生理感觉处理所必需的，并且我们确定星形胶质细胞 Sox9 是小鼠 OB 中成熟星形胶质细胞功能的重要转录调节因子。
