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研究发现小鼠大脑中的神经炎性星形胶质细胞亚型
2021-08-22 14:13

美国纽约大学Shane A. Liddelow、Philip Hasel等研究人员合作发现小鼠大脑中的神经炎性星形胶质细胞亚型。这一研究成果于2021年8月19日在线发表在国际学术期刊《自然—神经科学》上。

研究人员调查了使用细菌细胞壁内毒素脂多糖进行急性炎症刺激后小鼠皮质星形细胞的转录组变化。研究人员发现星形胶质细胞的快速转录组变化在几小时内发生,并随着时间的推移而急剧变化。通过对约80,000个星形胶质细胞进行单细胞分辨率测序,研究人员显示炎症会引起广泛的反应,星形胶质细胞的亚型会经历不同的炎症转变,并有明确的转录组图谱。研究人员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于特定的脑区。这一数据集为剖析星形细胞的异质性提供了强大的资源,并将有助于理解区域性限制的反应性星形细胞亚型的生物学重要性。

据介绍,星形胶质细胞在感染、急性损伤和慢性神经退行性疾病后会发生炎症性转变。这种转变如何受时间和性别的影响,它在单细胞水平上的异质性以及亚状态如何在大脑中的空间分布仍然不清楚。

附:英文原文

Title: Neuroinflammatory astrocyte subtypes in the mouse brain

Author: Hasel, Philip, Rose, Indigo V. L., Sadick, Jessica S., Kim, Rachel D., Liddelow, Shane A.

Issue&Volume: 2021-08-19

Abstract: 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. Using single-cell RNA sequencing and spatial transcriptomics, Hasel et al. uncover complex reactive astrocyte subtypes that occupy distinct areas of the brain. They find two super-responders expressing unique genes in strategic locations in the brain.

DOI: 10.1038/s41593-021-00905-6

Source: https://www.nature.com/articles/s41593-021-00905-6

Nature Neuroscience:《自然—神经科学》,创刊于1998年。隶属于施普林格·自然出版集团,最新IF:28.771
官方网址:https://www.nature.com/neuro/
投稿链接:https://mts-nn.nature.com/cgi-bin/main.plex


本期文章:《自然—神经科学》:Online/在线发表

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