Spatial genomics single cell analysis of aging brains

总结 我们最近展示了一种称为 seqFISH 的方法，该方法可以分析完整大脑中单个细胞中超过 10,000 个基因 样品。 seqFISH 的 mRNA 数量比现有方法提高 10 倍或更多 每个细胞的轮廓和条形码检测，提供了一种生成细胞空间图谱的方法。在这个项目中，我们 将在 P56、9 个月和 18 个月大的男性和女性的衰老大脑中应用 seqFISH。我们 将使用 seqFISH 数据来绘制细胞间信号相互作用及其对细胞命运决定的影响 直接在原地。凭借 seqFISH 的基因组覆盖度和空间分辨率，现在可以执行 独立于 scRNA-seq 的发现驱动研究，允许询问细胞中的分子过程 直接原位老化大脑。同时，我们将开发计算基础设施来理解 单细胞水平上不同发育时间点之间的过渡。这种极具创新性和 多学科方法将使我们能够系统地生成基于衰老大脑的空间图谱 解剖学和分子身份。这些合作努力将使我们能够打破技术壁垒 为大脑研究开发前所未有的全面开放资源。

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.