Center for multidimensional atlas of the human heart

项目总结--总体 人类心脏在解剖、细胞和功能上表现出显著的异质性，具有特殊的 细胞结构执行独特但基本的生理功能的细胞结构。一个重要的知识差距是 不同细胞的分子特征、空间分布和相互作用以及功能状态仍然很少 为了心灵而理解。因此，我们建议对心脏进行深入的描述，这解释了 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图 使用全面的多维单细胞和成像技术研究人类的寿命进程。这个 最终产品将以以下方式影响心脏研究：1)器官地图集：空间分辨率 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。分子数据将用更多的临床和 流行病学数据。2)计算方法：除了数据，关键的计算工具和 在这个项目中开发的管道将向研究界提供。其中包括方法和 处理多组学和成像数据的管道，细胞特异性调控和信号的推断 路径、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)获得用于后续行动的生物检疫制剂 研究：在这个项目中收集的生物样本将被储存起来，并提供给生物医学研究 社区。这些包括新鲜冷冻和固定的标本和组织切片。总括而言，建议的 该项目将广泛影响整个研究界，并推动基础科学和医学发现 基于对人体发育和衰老的关键分子回路的深入了解 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.