IRF8在产后微质中配置增强器景观,并指导微质特定的转录程序
Keita Saeki1, Richard Pan1,2, Eunju Lee1
1Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, 20892.
bioRxiv : the preprint server for biology
|August 30, 2023
概括
转录因子IRF8对于微质细胞发育至关重要,调节它们的基因表达和身份. 删除IRF8会损害微质功能,并减少阿尔茨海默病的小鼠模型中的病理.
科学领域:
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
背景情况:
- 微质细胞是大脑的先天免疫细胞.
- 转录因子IRF8在微质中高度表达,但其在产后发育中的作用尚不清楚.
研究的目的:
- 研究IRF8在产后微质发育和功能中的作用.
- 阐明微质中由IRF8调节的表观遗传机制.
主要方法:
- 染色体免疫沉测序 (ChIP-seq) 用于识别IRF8结合部位.
- 单细胞RNA测序 (scRNA-seq) 和单细胞对转化酶可访问染色体测序 (scATAC-seq) 的测试,以分析基因表达和染色体可访问性.
- 在野生型和缺少Irf8的小鼠中分析微质,包括5xFAD阿尔茨海默病模型.
主要成果:
- 在产后微细胞发育过程中,IRF8会逐步结合增强器区域,与增加的染色质可访问性和微细胞特异性基因表达相关.
- 删除IRF8会导致微质识别的丧失,获得与疾病相关的微质基因,并改变DNA甲基化模式.
- 在5xFAD模型中,Irf8缺失减少了微质与粉样质斑块的相互作用,减少了斑块大小,并减少了神经元损失.
结论:
- IRF8建立了对于产后微质细胞基因表达和身份至关重要的表观遗传景观.
- IRF8在调节微质功能和它们对神经退行性病理的反应方面发挥着关键作用.
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