Spatial genomics single cell analysis of aging brains

衰老大脑的空间基因组学单细胞分析

• 批准号: 10410511
• 负责人: Long Cai
• 金额: $ 86.81万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10410511
• 关键词: Age; Age-Months; Aging; Anatomy; Animals; Atlases; Bar Codes; Base of the Brain; Biological; Brain; Cell Communication; Cells; Data; Development; Female; Genes; Genome; Genomics; Goals; Hippocampus (Brain); Image; In Situ; Individual; Interneurons; Introns; Maps; Measurement; Messenger RNA; Meta-Analysis; Methods; Microscope; Microscopy; Modality; Molecular; Mus; Online Systems; Pattern; Population; Process; Proteins; Resolution; Resources; Sampling; Signal Transduction; Slice; Speed; Time; Tissues; Visualization; age effect; aging brain; brain research; cell type; cellular imaging; computational pipelines; computer infrastructure; computerized tools; data visualization; dentate gyrus; innovation; interdisciplinary approach; male; neuroblast; neurogenesis; new technology; novel; olfactory bulb; preservation; scale up; single cell analysis; single-cell RNA sequencing; tool; transcriptome

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.

概括 我们最近证明了一种称为seqfish+的方法，该方法在完整大脑中的单个细胞中含量> 10,000个基因 样品。 Seqfish+对MRNA数量的现有方法提供了10倍或更多的改进 每个细胞检测到的剖面和条形码，提供了一种生成细胞空间地图集的方法。在这个项目中，我们 男性和女性都将在p56、9个月和18个月大的p56、9个月和18个月以上应用seq鱼+。我们 将使用seqfish+数据来绘制细胞到细胞信号的交互及其对细胞命运决策的影响 直接原位。随着基因组覆盖范围和seqfish+的空间分辨率，现在可以执行 发现独立于SCRNA-SEQ的发现驱动的研究，允许对分子过程的询问 直接原位衰老的大脑。同时，我们将开发计算基础架构以了解 单个细胞水平的不同发育时间点之间的过渡。这种高度创新的 多学科的方法将使我们能够根据 解剖学和分子身份。这些协作努力将使我们能够打破技术障碍和 为大脑研究开发前所未有的全面开放资源。