Center for Developmental Mapping of Heart and Bone Tissues

项目概要 - 总体 人类骨骼和心脏都呈现出显着的解剖学、细胞和功能异质性， 特殊的细胞结构执行独特但重要的生理功能。差距显着 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 对于这两个器官仍然知之甚少。尽管在空间上是分离的，但越来越多的证据表明，骨 心脏通讯轴在这两个器官的正常发育和发病机制中起着至关重要的作用 可能还有其他器官。这两个器官的联合分析可以揭示对这两个器官的新见解 器官间通讯的微环境组织和信号通路。我们 因此，建议对这两个机构进行深入的描述，这两个机构加起来占了很大一部分。 人类疾病负担的一小部分。我们将绘制整个过程中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来研究人类的寿命。最终产品 将以下列方式影响这两个器官的研究： 1）器官图谱：空间解析图谱 将提供一个高度用户友好、公开可用、可搜索的最全面的多元数据库 组学，两个器官的单细胞分析。分子数据将通过额外的临床和 流行病学数据。 2）计算方法：除了数据之外，关键的计算工具和 该项目开发的管道将提供给研究界。这些包括方法和 用于处理多组学和成像数据、细胞特异性调控和信号传导的推断的管道 途径、介观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) 获取生物样本进行后续追踪 研究：该项目中收集的生物样本将被存储并可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。综上所述，建议 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 基于对发育和老化的关键分子电路的深入理解 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.