Abstract：
Microglial reactivity to injury and disease is emerging as a heterogeneous, dynamic, and crucial determinant in neurological disorders. However, the plasticity and fate of disease-associated microglia (DAM) remain largely unknown. We established a lineage tracing system, leveraging the expression dynamics of secreted phosphoprotein 1（Spp1） to label and track DAM-like microglia during brain injury and recovery. Fate mapping of Spp1+ microglia during stroke in juvenile mice revealed an irreversible state of DAM-like microglia that were ultimately eliminated from the injured brain. By contrast, DAM-like microglia in the neonatal stroke models exhibited high plasticity, regaining a homeostatic signature and integrating into the microglial network after recovery. Furthermore, neonatal injury had a lasting impact on microglia, rendering them intrinsically sensitized to subsequent immune challenges. Therefore, our findings highlight the plasticity and innate immune memory of neonatal microglia, shedding light on the fate of DAM-like microglia in various neuropathological conditions.
摘要：
小胶质细胞对损伤和疾病的反应性正在出现，动态,和神经系统疾病的关键决定因素。然而,疾病相关小胶质细胞(DAM)的可塑性和命运在很大程度上仍然未知.我们建立了血统追踪系统，利用分泌型磷蛋白1（Spp1）的表达动态来标记和跟踪脑损伤和恢复过程中的DAM样小胶质细胞。幼年小鼠中风期间Spp1小胶质细胞的命运图显示DAM样小胶质细胞的不可逆状态，最终从受伤的大脑中消除。相比之下,DAM样小胶质细胞在新生儿卒中模型中表现出高可塑性，恢复稳态特征并在恢复后整合到小胶质细胞网络中。此外，新生儿损伤对小胶质细胞有持久的影响，使它们对随后的免疫挑战具有内在的敏感性。因此,我们的发现强调了新生儿小胶质细胞的可塑性和先天免疫记忆，揭示了DAM样小胶质细胞在各种神经病理学条件下的命运。
