哺乳动物大脑发育和神经炎症的空间动态通过多式三组学绘制多式三组学绘制
Di Zhang1,2, Leslie A Rubio Rodríguez-Kirby3,2, Yingxin Lin4
1Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA.
bioRxiv : the preprint server for biology
|August 2, 2024
概括
这项研究使用空间三原子测序绘制了大脑发育和神经炎症的地图. 它揭示了发育和疾病中的共同分子程序,突出了微质细胞.
科学领域:
- 神经科学是一个神经科学.
- 基因组学就是基因组学.
- 分子生物学分子生物学
背景情况:
- 了解大脑发育和神经炎症需要在时间和空间上绘制多omics信息.
- 现有的技术往往缺乏空间分辨率或多原子能力来捕捉动态的大脑过程.
研究的目的:
- 开发和应用新的空间三原子测序技术,用于绘制动态大脑重塑的地图.
- 创建一个发育中的小鼠大脑的时空三原子地图,并将其与人类大脑发育进行比较.
- 为了研究神经炎症中的分子机制,使用柳索莱丁 (LPC) 鼠标模型.
主要方法:
- 空间三原子测序:DBiT ARP-seq (空间ATAC-RNA-蛋白质-seq) 和DBiT CTRP-seq (空间CUT&Tag-RNA-蛋白质-seq). 这两种测序是可以进行的.
- 多复合免疫光成像 (CODEX) 用于空间绘图.
- 对从产后日P0到P21的小鼠大脑发育的分析和lysolecithin诱导的神经炎症模型.
主要成果:
- 发现在皮层中层定义转录因子的染色质可访问性的时间持久性和空间扩散.
- 观察到大脑质体中髓基因的动态色素原始化,这表明轴突生成和髓化之间的协调.
- 鉴定出共同的分子程序,是大脑发育和神经炎症的基础,微质细胞在炎症和解决过程中发挥关键作用.
结论:
- 空间三原子测序提供了一种强大的方法来解开复杂的大脑过程.
- 共同和差异化的分子机制控制着大脑发育和神经炎症.
- 生成的时空地图集是未来大脑研究和疾病调查的宝贵资源.
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