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: 10020894
• 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/10020894
• 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.

总结 我们最近展示了一种名为seqFISH+的方法，该方法可以在完整大脑的单细胞中分析> 10，000个基因 样品与现有方法相比，seqFISH+在mRNA数量上提供了10倍或更多的改进 分析和检测每个细胞的条形码，提供了一种生成细胞空间图谱的方法。本课题 将在P56、9月龄和18月龄时对雄性和雌性的老化大脑应用seqFISH+。我们 将使用seqFISH+数据来绘制细胞与细胞之间的信号相互作用及其对细胞命运决定的影响 直接在原地。有了seqFISH+的基因组覆盖率和空间分辨率，现在可以执行 独立于scRNA-seq的发现驱动的研究，允许在基因组中询问分子过程， 直接在原位老化大脑。与此同时，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。这一高度创新和 多学科的方法将使我们能够系统地生成一个空间地图集的老龄化大脑的基础上， 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。