Center for Developmental Mapping of Heart and Bone Tissues

项目总结--总体 人类的骨骼和心脏在解剖、细胞和功能上都表现出显著的异质性， 特殊的细胞结构，具有独特而基本的生理功能。差距很大， 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，人们仍然知之甚少。尽管在空间上是分开的，但越来越多的证据表明，一块骨头- 心脏通信轴在这两个器官的正常发育和发病机制中起着关键作用。 可能还有其他器官。对这两个器官的联合分析可以揭示对 器官间交流的微环境、组织和信号通路。我们 因此，建议对这两个器官进行深入的描述，这两个器官加在一起，占了很大的比例 人类疾病负担的一小部分。我们将绘制组织中分子和细胞的变化图 使用全面的多维单细胞和成像技术延长人类寿命。最终产品 将对这两个器官的研究产生以下影响：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、最全面的多- 对这两个器官进行基因组、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 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.