Brain region- and sex-specific transcriptional profiles of microglia.
Brain region- and sex-specific transcriptional profiles of microglia.
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DOI：
10.3389/fpsyt.2022.945548
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发表时间：
2022
影响因子：
4.7
通讯作者：
Seney, Marianne L.
中科院分区：
文献类型：
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作者：
Barko, Kelly;Shelton, Micah;Xue, Xiangning;Afriyie-Agyemang, Yvette;Puig, Stephanie;Freyberg, Zachary;Tseng, George C.;Logan, Ryan W.;Seney, Marianne L.
小胶质细胞是脑的常驻巨噬细胞，执行与脑稳态相关的作用，包括突触的调节、营养支持、凋亡细胞和碎片的吞噬作用以及脑保护和修复。评估小胶质细胞的形态和转录特征的研究发现，在一些研究的大脑区域中存在区域差异和性别差异。然而，在许多先前的研究中用于分离小胶质细胞的标记物并不完全由小胶质细胞表达，或者不能用于在所有情况下鉴定和分离小胶质细胞。在这里，荧光激活细胞分选用于分离表达小胶质细胞特异性标记TMEM 119的细胞，来自小鼠的前额叶皮层（PFC）、纹状体和中脑。RNA测序用于评估小胶质细胞的转录谱，重点是脑区域和性别差异。我们发现了小胶质细胞特异性转录表达的显著脑区差异。最值得注意的是中脑小胶质细胞独特的转录谱，富集了与免疫功能相关的途径;这些中脑小胶质细胞表现出与疾病相关或免疫监视小胶质细胞相似的谱。PFC分离的小胶质细胞中表达更高的转录本富集了突触相关通路，而从纹状体分离的小胶质细胞富集了微管聚合相关通路。我们还发现了证据表明，小胶质细胞特异性转录物的表达梯度横跨大脑的喙尾轴，从纹状体提取的小胶质细胞表现出PFC和中脑之间的转录谱。我们还发现，在所有3个大脑区域中，小胶质细胞特异性转录物的表达存在性别差异，许多硒相关转录物在女性大脑区域中的表达更高。这些结果表明，在稳态条件下，小胶质细胞的转录谱在大脑区域之间存在差异，这表明小胶质细胞在不同的大脑区域中发挥着不同的作用，甚至基于性别。
Microglia are resident macrophages of the brain, performing roles related to brain homeostasis, including modulation of synapses, trophic support, phagocytosis of apoptotic cells and debris, as well as brain protection and repair. Studies assessing morphological and transcriptional features of microglia found regional differences as well as sex differences in some investigated brain regions. However, markers used to isolate microglia in many previous studies are not expressed exclusively by microglia or cannot be used to identify and isolate microglia in all contexts. Here, fluorescent activated cell sorting was used to isolate cells expressing the microglia-specific marker TMEM119 from prefrontal cortex (PFC), striatum, and midbrain in mice. RNA-sequencing was used to assess the transcriptional profile of microglia, focusing on brain region and sex differences. We found striking brain region differences in microglia-specific transcript expression. Most notable was the distinct transcriptional profile of midbrain microglia, with enrichment for pathways related to immune function; these midbrain microglia exhibited a profile similar to disease-associated or immune-surveillant microglia. Transcripts more highly expressed in PFC isolated microglia were enriched for synapse-related pathways while microglia isolated from the striatum were enriched for pathways related to microtubule polymerization. We also found evidence for a gradient of expression of microglia-specific transcripts across the rostral-to-caudal axes of the brain, with microglia extracted from the striatum exhibiting a transcriptional profile intermediate between that of the PFC and midbrain. We also found sex differences in expression of microglia-specific transcripts in all 3 brain regions, with many selenium-related transcripts more highly expressed in females across brain regions. These results suggest that the transcriptional profile of microglia varies between brain regions under homeostatic conditions, suggesting that microglia perform diverse roles in different brain regions and even based on sex.
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影响因子：
3.8
作者：
Chung, Youn Wook;Jeong, Daewon;Kim, Ick Young
通讯作者：
Kim, Ick Young
影响因子：
4.6
作者：
Furube E;Kawai S;Inagaki H;Takagi S;Miyata S
通讯作者：
Miyata S
影响因子：
4.6
作者：
Cahill KM;Huo Z;Tseng GC;Logan RW;Seney ML
通讯作者：
Seney ML
影响因子：
3.8
作者：
Bramlett, KS;Burris, TP
通讯作者：
Burris, TP
影响因子：
30.5
作者：
通讯作者：
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