Center for Developmental Mapping of Heart and Bone Tissues

项目概要-总体 人类骨骼和心脏都存在显著的解剖、细胞和功能异质性， 特殊的细胞结构，执行独特而重要的生理功能。一个巨大的差距 知识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 对这两个机构的了解仍然很少。尽管在空间上是分开的，但越来越多的证据表明- 心脏通讯轴在这两个器官的正常发育和发病中起着关键作用 可能还有其他器官对这两种器官的联合分析可能会揭示对这一问题的新见解。 微环境组织和信号通路的基础上的器官间的通信。我们 因此，建议对这两个器官进行深入表征，这两个器官加在一起占了很大一部分 人类疾病负担的一部分。我们将绘制组织中分子和细胞的变化， 人类寿命使用全面的多维单细胞和成像技术。最终产品 将以以下方式影响这两个器官的研究：1）器官图谱：空间分辨图谱 将提供一个高度用户友好的，公开的，最全面的多搜索数据库， 两个器官的组学、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， 这两个器官。

PROJECT SUMMARY - OVERALL Both human bone and heart present 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 both organs. Although spatially separated, growing evidence suggests that a bone- heart communication axis plays a critical role in normal development and pathogenesis of these two organs and possibly other organs. Joint analysis of the two organs could reveal novel insights into the microenvironment organization and signaling pathways underlying the inter-organ communication. We therefore propose the in-depth characterization of these two organs which, together, account for a large fraction of human disease burden. We will map molecular and cellular changes in the tissue over the course of human lifespan using comprehensive multi-dimensional single-cell and imaging technologies. The final product will impact research of these two organs 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 two organs. 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 these two organs.