Spatial genomics single cell analysis of aging brains

摘要 我们最近演示了一种名为seqFISH的方法，它可以在完整大脑的单个细胞中分析&>10,000个基因 样本。SeqFISH在mRNAs的数量上比现有方法提高了10倍或更多 每个单元检测到的轮廓和条形码，提供了一种生成单元空间图谱的方法。在这个项目中，我们 将SeqFISH应用于P56、9个月和18个月龄的男性和女性老化的大脑。我们 将使用seqFISH数据来绘制细胞间的信号相互作用及其对细胞命运决定的影响 直接就地。有了seqFISH的基因组覆盖和空间分辨率，现在可以进行 发现驱动的研究独立于scRNA-seq，允许询问分子过程 直接在原位老化大脑。同时，我们将开发计算基础设施，以了解 在单细胞水平上不同发育时间点之间的过渡。这一极具创新性的 多学科方法将使我们能够系统地生成老化大脑的空间图谱，基于 解剖学和分子同一性。这些合作努力将使我们能够打破技术障碍， 开发空前全面的脑研究开放资源。

Summary We recently demonstrated a method called seqFISH+ that profiles >10,000 genes in single cells in intact brain samples. seqFISH+ provides 10-fold or more improvement over existing methods in the number of mRNAs profiled and barcodes detected per cell, providing a method to generate spatial atlas of cell. In this project, we will apply seqFISH+ to the aging brain at P56, 9 month and 18 month of age for both males and females. We will use the seqFISH+ data to map out cell-to-cell signaling interactions and their effects on cell fate decisions directly in situ. With the genome coverage and spatial resolution of seqFISH+, it is now possible to perform discovery-driven studies independent of scRNA-seq, allowing the interrogation of molecular processes in the aging brain directly in situ. At the same time, we will develop the computational infrastructure to understand the transition between different developmental time points at the single cell level. This highly innovative and multidisciplinary approach will allow us to systematically generate a spatial atlas of the aging brain based on anatomy and molecular identities. These collaborative efforts will allow us to break technological barriers and develop an unprecedentedly comprehensive open resource for brain research.