Center for multidimensional atlas of the human heart

项目概要-总体 人类心脏呈现出显著的解剖学、细胞和功能异质性， 细胞结构执行不同但基本的生理功能。一个重大的知识差距是 不同细胞的分子特征，空间分布和相互作用，以及功能状态几乎没有 理解为心。因此，我们建议深入表征的心脏，其中占一个 人类疾病负担的很大一部分。我们将绘制心脏组织的分子和细胞变化， 使用全面的多维单细胞和成像技术来观察人类的寿命过程。的 最终产品将以以下方式影响心脏研究：1）器官解剖：空间分辨 地图集将提供一个高度用户友好的、公开可用的、可搜索的最全面的数据库， 心脏的多组单细胞分析。分子数据将用额外的临床和生物学方法进行丰富的注释。 流行病学数据。2)计算方法：除了数据，关键的计算工具和 该项目开发的管道将提供给研究界。其中包括方法和 用于处理多组学和成像数据、推断细胞特异性调节和信号传导的管道 途径，中尺度成像和分子成像特征的相关性，以及数据库算法 用于高度复杂数据的查询、探索和可视化。3)获取生物样本进行随访 研究：本项目收集的生物标本将被储存起来，供生物医学研究使用。 社区这些包括新鲜冷冻和固定的标本和组织切片。总之，拟议的 该项目将广泛影响整个研究界，并启动基础科学和医学发现 基于对发育和衰老的关键分子电路的复杂理解， 心脏

PROJECT SUMMARY - OVERALL The human heart presents remarkable anatomical, cellular and functional heterogeneity, with specialized cellular structures performing distinct yet essential physiological functions. A significant gap of knowledge is that different cells’ molecular signature, spatial distribution and interactions, and functional state remain little understood for the heart. We therefore propose the in-depth characterization of the heart which accounts for a large fraction of human disease burden. We will map molecular and cellular changes in heart tissues over the course of human lifespan using comprehensive multi-dimensional single-cell and imaging technologies. The final product will impact research of the heart in the following manner: 1) Organ Atlases: spatially resolved atlases will provide a highly user friendly, publicly available, searchable database of the most comprehensive multi-omic, single cell analysis of the heart. Molecular data will be richly annotated with additional clinical and epidemiological data. 2) Computational methods: in addition to the data, the critical computational tools and pipelines developed in this project will be available to the research community. These include methods and pipelines for processing multi-omics and imaging data, inference of cell-specific regulatory and signaling pathways, correlation of mesoscale imaging and molecular imaging features, as well as database algorithms for the query, exploration and visualization of highly complex data. 3) Access to biospecimens for follow-up studies: biospecimens collected in this project will be banked and made available to the biomedical research community. These include freshly frozen and fixed specimens and tissue sections. In summary, the proposed project will broadly impact the entire research community and jumpstart basic-science and medical discoveries based on a sophisticated understanding of the key molecular circuits underlying the development and aging of the heart.