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: 10196928
• 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/10196928
• 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.

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