A Spatially Resolved Molecular Atlas of Human Endothelium

摘要-总体 我们建议建立加州理工大学-华盛顿大学组织绘图中心（TMC），作为该组织绘图中心之一 人类生物分子图谱计划（Human BioMolecular Atlas Program，HuBMAP）TMC的首要目标是生成 高分辨率，高内容的非患病人体器官和系统的多尺度地图。为此我们 我建议成立一个TMC，将多路空间转录组学领先技术的开发人员聚集在一起 (Long Cai，seqFISH）和用于染色质可及性的单细胞谱分析的超可扩展方法， 转录组（Shendure和Trapnell，sci-ATAC-seq和sci-RNA-seq）。通过一个器官特异性项目 (OSP)，我们描述了一个管道，以收集高质量的，正常的人类样本，并明确同意开放 访问基因组数据共享（GDS）并分发给联盟成员。我们将描述和量化 人体循环系统的分子异质性与其解剖结构的多个方面有关， 分布，包括器官特异性异质性，器官内地带性，下至细胞间异质性。 通过一种迭代方法，包括通过seqFISH和解聚细胞分析空间完整的组织 通过sci-ATAC-seq和sci-RNA-seq，我们将获得一个空间分辨的，全面的分子画像， 染色质可及性和基因表达在人体循环系统中的作用。通过偶然 收集，我们预计产生的表达和染色质可及性数据的各种细胞类型，在所有 我们调查的器官，这将提供重要信息，并增加其他机构收集的数据集的价值。 TMC和OSP。我们将与其他TMC和更广泛的HuBMAP计划密切合作， 共享和整合数据和方法，最终建立一个广泛有用的平台， 以高分子和解剖学分辨率了解人体器官和系统。

ABSTRACT - OVERALL We propose to establish the Caltech-UW Tissue Mapping Center (TMC), which will serve as one of the T​MCs of the NIH’s Human BioMolecular Atlas Program (HuBMAP). The overarching goal of the TMCs is to generate high-resolution, high-content multiscale maps of non-diseased human organs and systems. To this end, we propose a TMC that brings together the developers of leading technologies for multiplex spatial transcriptomics (Long Cai, seqFISH) and ultra-scalable methods for single cell profiling of chromatin accessibility and transcriptomes (Shendure & Trapnell, sci-ATAC-seq and sci-RNA-seq). Through an organ specific project (OSP), we describe a pipeline to collect high quality, normal human samples with explicit consent for open access genome data sharing (GDS) and distribution to consortium members. We will characterize and quantify the molecular heterogeneity of the human circulatory system in relation to multiple facets of its anatomical distribution, including organ-specific heterogeneity, intra-organ zonality, down to cell-to-cell heterogeneity. Through an iterative approach involving profiling of spatially intact tissues by seqFISH and disaggregated cells by sci-ATAC-seq and sci-RNA-seq, we will obtain a spatially resolved, comprehensive molecular portrait of both chromatin accessibility and gene expression across the human circulatory system. Through incidental collection, we anticipate generating expression and chromatin accessibility data for diverse cell types in all organs that we survey, which will critically inform and increase the value of the datasets collected by other TMCs and OSPs. We will work closely and openly with the other TMCs and the broader HuBMAP program to share and integrate data as well as methods and ultimately build a broadly useful platform for exploring and understanding human organs and systems at high molecular and anatomical resolution.