Definition of a mouse microglial subset that regulates neuronal development and pro-inflammatory responses in the brain

Expression of Itgax (encoding the CD11c surface protein) and Spp1 (encoding OPN) have been associated with activated microglia that can develop in healthy brains and some neuroinflammatory disorders. Here, we show that OPN production in the brain is confined to a small CD11c+ microglial subset that differentiates from CD11c- precursors in perinatal life after uptake of apoptotic neurons. Our analysis suggests that co-expression of OPN and CD11c genes marks a microglial subset that is expressed at birth and persists into late adult life, independent of environmental activation stimuli. Definition of OPN-producing CD11c+ microglia as a functional microglial subset provides new insight into microglial differentiation in health and disease. Microglial mRNA profiles of CD11c+ subset versus CD11c- subset in postnatal day 5 (P5), 9-month old wild type (WT) mice.整合素αX（Itgax，编码CD11c表面蛋白）与分泌型磷蛋白1（Spp1，编码骨桥蛋白OPN）的表达，已被证实与活化小胶质细胞相关——这类细胞可在健康大脑及部分神经炎性疾病中出现。本研究证实，大脑内的骨桥蛋白（OPN）产生仅局限于一小群CD11c阳性（CD11c+）小胶质细胞亚群；该亚群在围产期摄取凋亡神经元后，由CD11c阴性（CD11c-）前体细胞分化而来。我们的分析显示，骨桥蛋白（OPN）与CD11c基因的共表达，可作为一类小胶质细胞亚群的标记：该亚群在出生时即已存在，并可持续至成年晚期，且不依赖于环境活化刺激。将产骨桥蛋白的CD11c+小胶质细胞定义为功能性小胶质细胞亚群，为健康与疾病状态下的小胶质细胞分化研究提供了全新视角。本数据集涵盖出生后第5天（P5）、9月龄野生型（WT）小鼠的CD11c+与CD11c-小胶质细胞亚群的mRNA表达谱。