西湖大学何丹阳等研究人员合作发现，Spp1表达的命运图谱揭示脑损伤后与疾病相关的小胶质细胞的年龄可塑性。2024年2月2日，国际知名学术期刊《免疫》在线发表了这一成果。

研究人员利用分泌型磷蛋白1（Spp1）的表达动态，建立了一个谱系追踪系统，以标记和追踪疾病相关小胶质细胞（DAM）样小胶质细胞。Spp1⁺小胶质细胞在幼鼠中风期间的命运图谱显示了DAM样小胶质细胞的不可逆状态，它们最终会从受伤的大脑中被清除。相比之下，新生儿中风模型中的DAM样小胶质细胞表现出高度的可塑性，在恢复后能重新获得平衡特征并融入小胶质细胞网络。

此外，新生儿损伤会对小胶质细胞产生持久影响，使它们对随后的免疫挑战产生内在敏感性。因此，这些研究结果突显了新生儿小胶质细胞的可塑性和先天免疫记忆，并揭示了DAM样小胶质细胞在各种神经病理学条件下的命运。

研究人员表示，小胶质细胞对损伤和疾病的反应正在成为神经系统疾病中一个异质性、动态和关键的决定因素。然而，DAM的可塑性和命运在很大程度上仍然未知。

附：英文原文

Title: Fate mapping of Spp1 expression reveals age-dependent plasticity of disease-associated microglia-like cells after brain injury

Author: Yangning Lan, Xiaoxuan Zhang, Shaorui Liu, Chen Guo, Yuxiao Jin, Hui Li, Linyixiao Wang, Jinghong Zhao, Yilin Hao, Zhicheng Li, Zhaoyuan Liu, Florent Ginhoux, Qi Xie, Heping Xu, Jie-Min Jia, Danyang He

Issue&Volume: 2024-02-02

Abstract: Microglial reactivity to injury and disease is emerging as a heterogeneous, dynamic,and crucial determinant in neurological disorders. However, the plasticity and fateof disease-associated microglia (DAM) remain largely unknown. We established a lineagetracing system, leveraging the expression dynamics of secreted phosphoprotein 1（Spp1） to label and track DAM-like microglia during brain injury and recovery. Fate mappingof Spp1+ microglia during stroke in juvenile mice revealed an irreversible state of DAM-likemicroglia that were ultimately eliminated from the injured brain. By contrast, DAM-likemicroglia in the neonatal stroke models exhibited high plasticity, regaining a homeostaticsignature and integrating into the microglial network after recovery. Furthermore,neonatal injury had a lasting impact on microglia, rendering them intrinsically sensitizedto subsequent immune challenges. Therefore, our findings highlight the plasticityand innate immune memory of neonatal microglia, shedding light on the fate of DAM-likemicroglia in various neuropathological conditions.

DOI: 10.1016/j.immuni.2024.01.008

Source: https://www.cell.com/immunity/fulltext/S1074-7613(24)00032-3