Neuroinflammatory astrocyte subtypes in the mouse brain
Neuroinflammatory astrocyte subtypes in the mouse brain
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DOI：
10.1038/s41593-021-00905-6
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发表时间：
2021-08-19
影响因子：
25
通讯作者：
Liddelow, Shane A.
中科院分区：
文献类型：
--
作者：
Hasel, Philip;Rose, Indigo V. L.;Liddelow, Shane A.
星形胶质细胞在感染、急性损伤和慢性神经退行性疾病后经历炎症转变。这种转变如何受到时间和性别的影响、其在单细胞水平上的异质性以及亚状态在大脑中的空间分布如何仍不清楚。在这项研究中，我们利用细菌细胞壁内毒素脂多糖研究了小鼠皮质星形胶质细胞在急性炎症刺激后转录组的变化。我们发现星形胶质细胞在数小时内发生快速转录组变化，并且随着时间的推移而发生巨大变化。通过以单细胞分辨率对 80,000 个星形胶质细胞进行类似的测序，我们发现炎症会引起广泛的反应，星形胶质细胞亚型经历具有明确转录组谱的不同炎症转变。我们还利用空间转录组学和原位杂交将炎症诱导的反应性星形胶质细胞的关键亚状态归因于特定的大脑区域。总之，我们的数据集为分析星形胶质细胞异质性提供了强大的资源，并将有助于理解区域受限的反应性星形胶质细胞亚状态的生物学重要性。
Astrocytes undergo an inflammatory transition after infections, acute injuries and chronic neurodegenerative diseases. How this transition is affected by time and sex, its heterogeneity at the single-cell level and how sub-states are spatially distributed in the brain remains unclear. In this study, we investigated transcriptome changes of mouse cortical astrocytes after an acute inflammatory stimulus using the bacterial cell wall endotoxin lipopolysaccharide. We identified fast transcriptomic changes in astrocytes occurring within hours that drastically change over time. By sequencing similar to 80,000 astrocytes at single-cell resolution, we show that inflammation causes a widespread response with subtypes of astrocytes undergoing distinct inflammatory transitions with defined transcriptomic profiles. We also attribute key sub-states of inflammation-induced reactive astrocytes to specific brain regions using spatial transcriptomics and in situ hybridization. Together, our datasets provide a powerful resource for profiling astrocyte heterogeneity and will be useful for understanding the biological importance of regionally constrained reactive astrocyte sub-states.