The embryonic ectoderm development (EED) is a core component of the polycomb-repressive complex 2 (PRC2) whose mutations are linked to neurodevelopmental abnormalities, intellectual disability, and neurodegeneration. Although EED has been extensively studied in neural stem cells and oligodendrocytes, its role in microglia is incompletely understood. Here, we show that microglial EED is essential for synaptic pruning during the postnatal stage of brain development. The absence of microglial EED at early postnatal stages resulted in reduced spines and impaired synapse density in the hippocampus at adulthood, accompanied by upregulated expression of phagocytosis-related genes in microglia. As a result, deletion of microglial Eed impaired hippocampus-dependent learning and memory in mice. These results suggest that microglial EED is critical for normal synaptic and cognitive functions during postnatal development.
基金:
National Key Research and Development Program of China [2018YFA0108001/2021YFA1101402]; Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16010300]; National Science Foundation of China [32170808]; Open Project Program of State Key Laboratory of Stem Cell and Reproductive Biology
第一作者机构:[1]Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China[2]Univ Chinese Acad Sci, Savaid Med Sch, Beijing 100049, Peoples R China[3]Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China[4]Teijing Inst Stem Cell & Regenerat Med, Beijing 100101, Peoples R China
通讯作者:
通讯机构:[1]Chinese Acad Sci, Inst Zool, State Key Lab Stem Cell & Reprod Biol, Beijing 100101, Peoples R China[2]Univ Chinese Acad Sci, Savaid Med Sch, Beijing 100049, Peoples R China[3]Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China[4]Teijing Inst Stem Cell & Regenerat Med, Beijing 100101, Peoples R China
推荐引用方式(GB/T 7714):
Wang Ying-Ying,Deng Yu-Sen,Dai Shang-Kun,et al.Loss of microglial EED impairs synapse density, learning, and memory[J].MOLECULAR PSYCHIATRY.2022,27(7):2999-3009.doi:10.1038/s41380-022-01576-w.
APA:
Wang, Ying-Ying,Deng, Yu-Sen,Dai, Shang-Kun,Mi, Ting-Wei,Li, Rui-Yang...&Teng, Zhao-Qian.(2022).Loss of microglial EED impairs synapse density, learning, and memory.MOLECULAR PSYCHIATRY,27,(7)
MLA:
Wang, Ying-Ying,et al."Loss of microglial EED impairs synapse density, learning, and memory".MOLECULAR PSYCHIATRY 27..7(2022):2999-3009