Defining the pig microglial transcriptome reveals its core signature, regional heterogeneity, and similarity with human and rodent microglia.
Defining the pig microglial transcriptome reveals its core signature, regional heterogeneity, and similarity with human and rodent microglia.
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DOI：
10.1002/glia.24274
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发表时间：
2023-02
期刊：
影响因子：
6.2
通讯作者：
McColl, Barry W.
中科院分区：
文献类型：
--
作者：
Shih, Barbara B.;Brown, Sarah M.;Barrington, Jack;Lefevre, Lucas;Mabbott, Neil A.;Priller, Josef;Thompson, Gerard;Lawrence, Alistair B.;McColl, Barry W.
小胶质细胞在脑内环境稳定以及对由身体疾病和心理社会应激引起的神经变性和神经炎症过程的反应中起关键作用。猪是研究人类神经系统疾病的生理学相关模型物种，其中许多与小胶质细胞功能障碍有关。此外，猪是一种重要的农业物种，有必要了解小胶质细胞功能如何影响它们的福利。作为提高理解以加强生物医学和农业研究的基础，我们试图在全基因组范围内表征猪小胶质细胞身份并进行种间比较。我们从额叶皮质、海马和小脑分离猪海马组织和小胶质细胞，以及从肺分离肺泡巨噬细胞，并进行RNA测序（RNAseq）。通过比较小胶质细胞、巨噬细胞和海马组织之间的转录组学特征，我们推导出一组定义猪核心小胶质细胞特征的239个高度富集的基因。我们发现基于150个基因的大脑区域异质性显示出显著的（校正p < 0.01）区域变化，并且小脑小胶质细胞最明显。我们使用来自每个物种的小胶质细胞标记基因列表比较了来自人，小鼠和猪的小胶质细胞的标准化基因表达，并证明了核心小胶质细胞标记基因标记在物种间是保守的，但也存在物种特异性表达子集。我们的数据提供了一个有价值的资源，定义了猪小胶质细胞转录组签名，验证和突出猪作为一个有用的大型动物物种之间的桥梁啮齿动物和人类，其中研究小胶质细胞在稳态和疾病的作用。定义了包含239个基因的猪小胶质细胞转录组标签。证明了猪小胶质细胞转录组在整个大脑中的区域差异。揭示了猪小胶质细胞基因表达与人类和小鼠小胶质细胞基因表达的相似性。
Microglia play key roles in brain homeostasis as well as responses to neurodegeneration and neuroinflammatory processes caused by physical disease and psychosocial stress. The pig is a physiologically relevant model species for studying human neurological disorders, many of which are associated with microglial dysfunction. Furthermore, pigs are an important agricultural species, and there is a need to understand how microglial function affects their welfare. As a basis for improved understanding to enhance biomedical and agricultural research, we sought to characterize pig microglial identity at genome‐wide scale and conduct inter‐species comparisons. We isolated pig hippocampal tissue and microglia from frontal cortex, hippocampus, and cerebellum, as well as alveolar macrophages from the lungs and conducted RNA‐sequencing (RNAseq). By comparing the transcriptomic profiles between microglia, macrophages, and hippocampal tissue, we derived a set of 239 highly enriched genes defining the porcine core microglial signature. We found brain regional heterogeneity based on 150 genes showing significant (adjusted p < 0.01) regional variations and that cerebellar microglia were most distinct. We compared normalized gene expression for microglia from human, mice and pigs using microglia signature gene lists derived from each species and demonstrated that a core microglial marker gene signature is conserved across species, but that species‐specific expression subsets also exist. Our data provide a valuable resource defining the pig microglial transcriptome signature that validates and highlights pigs as a useful large animal species bridging between rodents and humans in which to study the role of microglia during homeostasis and disease. Defined a pig microglial transcriptome signature comprising 239 genes. Demonstrated regional variance in the pig microglial transcriptome across the brain. Revealed similarity of pig microglial gene expression to that of human and mouse microglia.
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影响因子：
25
作者：
Galatro, Thais F.;Holtman, Inge R.;Eggen, Bart J. L.
通讯作者：
Eggen, Bart J. L.
影响因子：
5.4
作者：
Freeman TC;Ivens A;Baillie JK;Beraldi D;Barnett MW;Dorward D;Downing A;Fairbairn L;Kapetanovic R;Raza S;Tomoiu A;Alberio R;Wu C;Su AI;Summers KM;Tuggle CK;Archibald AL;Hume DA
通讯作者：
Hume DA
DOI：
10.1084/jem.20202717
发表时间：
2021-09-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen Y;Colonna M
通讯作者：
Colonna M
DOI：
10.1073/pnas.1507125112
发表时间：
2015-06-09
影响因子：
11.1
作者：
Darmanis S;Sloan SA;Zhang Y;Enge M;Caneda C;Shuer LM;Hayden Gephart MG;Barres BA;Quake SR
通讯作者：
Quake SR
影响因子：
32.4
作者：
Hammond, Timothy R.;Dufort, Connor;Stevens, Beth
通讯作者：
Stevens, Beth