Hammond Brady P, Zia Sameera, Hahn Eugene, Kapustina Margarita, Lange Tristan, Friesen Sarah, Manek Rupali, Lee Kelly V, Castellanos-Molina Adrian, Bretheau Floriane, Cembrowski Mark S, Kerr Bradley J, Lacroix Steve, Plemel Jason R
Neuroscience and Mental Health Institute, University of Alberta, Edmonton, T6G 2R3, Canada.
Department of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, V6T 1Z3, Canada.
Development. 2025 Oct 15;152(20). doi: 10.1242/dev.204610. Epub 2025 Jun 3.
Microglia - the predominant immune cells of the brain and spinal cord - perform essential functions for the development and maintenance of the central nervous system, contingent upon the regulated developmental proliferation of microglia. However, the factor(s) that regulate microglial proliferation remain unclear. Here, we confirmed the timeline of developmental proliferation and used bioinformatics to identify potential signalling onto microglia in mouse from datasets collected at an age of high developmental microglial proliferation. Of the predicted factors, we found that colony stimulating factor 1 receptor (CSF1R) ligands boosted proliferation in vitro and were increasingly expressed in the brain across development with each displaying a distinct regional and temporal expression pattern. However, we did not observe a coincident alteration to CSF1R ligand levels in a model of abnormal developmental proliferation. Together, although CSF1R ligands can promote microglial proliferation in culture, their developmental expression patterns suggest that they function alongside other unknown factors to regulate developmental microglial proliferation.
小胶质细胞——脑和脊髓中的主要免疫细胞——对中枢神经系统的发育和维持起着至关重要的作用,这取决于小胶质细胞受调控的发育增殖。然而,调节小胶质细胞增殖的因素仍不清楚。在这里,我们确定了发育增殖的时间线,并利用生物信息学从发育中小胶质细胞增殖高峰期收集的小鼠数据集中识别出可能作用于小胶质细胞的信号。在预测的因素中,我们发现集落刺激因子1受体(CSF1R)配体在体外可促进增殖,并且在整个发育过程中在脑中表达增加,每个配体都显示出独特的区域和时间表达模式。然而,在异常发育增殖模型中,我们未观察到CSF1R配体水平的相应改变。总之,虽然CSF1R配体可在培养中促进小胶质细胞增殖,但其发育表达模式表明它们与其他未知因素共同作用来调节发育中小胶质细胞的增殖。