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

深入了解衰老的分子基础是开发诊断和治疗方法以减轻年龄相关疾病的关键。然而，创造一种通用年龄灵丹妙药的困难之一是，生物体中的每个细胞的年龄都是不同的。因此，衰老研究的目标之一是描述单个细胞如何随时间变化。这个项目将重点放在肌肉细胞上，因为肌肉无力是老年人的常见病。单细胞研究通常是困难的，因为源材料很少。测序和细胞收集技术的进步为单细胞基因组的研究提供了机会。该研究项目利用了横滨理研的设施来获取最新的单细胞技术，并受益于Aki Minoda博士的领导。本项目的目的是开发转座酶可及染色质测序（snATAC-seq）协议的单核检测，以表征小鼠骨骼肌的表观遗传异质性。虽然单细胞ATAC-seq是可用的，但可行的snATAC-seq仍未开发。ATAC-seq是一种测定表观遗传染色质修饰状态的新方法。与其他形式的测序不同，ATAC-seq能够绘制核小体位置，从而提供细胞表观基因组的多维描述。将这项有前途的技术应用于衰老和与衰老有关的疾病问题，开辟了新的论述途径和可能的治疗方法。单核ATAC-seq的发展消除了ATAC-seq固有的大小限制，并将开辟许多其他疾病状态下各种细胞类型的研究。该奖项由美国国家科学基金会和日本科学促进会共同资助，隶属于东亚和太平洋暑期研究所项目，支持一名美国研究生进行暑期研究。

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.