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 ~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.

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，其在单细胞水平的异质性以及亚状态在大脑中的空间分布方式仍不清楚。在这项研究中，我们使用细菌细胞壁内毒素脂多糖研究了急性炎症刺激后小鼠皮质星形胶质细胞的转录组变化。我们确定了星形胶质细胞在数小时内发生的快速转录组变化，这些变化随着时间的推移而发生巨大变化。通过以单细胞分辨率对约 80,000 个星形胶质细胞进行测序，我们发现炎症会引起广泛的反应，其中星形胶质细胞的亚型经历不同的炎症转变，并具有明确的转录组学特征。我们还使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。