EAPSI: Developing Single Nucleus ATAC-seq to Map the Ageing Epigenome

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Insights into the molecular basis of aging are key to developing diagnostic and therapeutic methods for alleviating age-related disorders. However, one of the difficulties in creating a general age panacea is the fact that each cell within an organism ages differently. Therefore, one of the goals for aging research is to characterize how individual cells change over time. This project will focus on muscle cells because muscle weakness is a common complaint in the elderly. Single cell studies are usually difficult due to the small amount of source material. Advances in sequencing and cell collection technology provide an opportunity for research into single cell genomes. This research project utilizes facilities at RIKEN Yokohama to access the latest in single cell technologies and to benefit from the leadership of Dr. Aki Minoda.The purpose of this project is to develop a single nucleus Assay for Transposase-Accessible Chromatin sequencing (snATAC-seq) protocol for the characterization of epigenetic heterogeneity in mouse skeletal muscle. While single cell ATAC-seq is available, viable snATAC-seq remains undeveloped. ATAC-seq is a novel method to determine the status of epigenetic chromatin modifications. Unlike other forms of sequencing, ATAC-seq is able to map nucleosome positions, thereby providing a multidimensional description of the cellular epigenome. Application of this promising technology to the question of ageing and ageing-related disease opens up new avenues of discourse and possible therapeutics. Development of single nucleus ATAC-seq ablates the size restriction inherent in ATAC-seq and will open up research in a variety of cell types in numerous other disease states. This award, under the East Asia and Pacific Summer Institutes program, supports summer research by a U.S. graduate student and is jointly funded by NSF and the Japan Society for the Promotion of Science.