Unbiased visualization of human ASC subsets

摘要： 浆细胞(PC)负责维持血清中对病原体的抗体水平。然而，a 目前还缺乏人体各组织间PC亚群的综合空间图。作为一名 因此，我们对个人内部不同组织中全球PC种群结构的理解 而不同个体之间的关系也是模糊的。利用独特而难得的人体组织资源 与高维流式细胞术一起，将检验PC亚集组成可以是 根据组织部位预测，长寿PC(LLPC)采用为每个部位量身定做的生存计划 原产地。在目标1中，我们将从正常人的淋巴和粘膜组织中鉴定已知和新的PC亚群 人类捐献者使用复杂的流式细胞术和无偏计算算法。我们将整合 表型与信号状态，并建立PC的功能能力。在《目标2》中，我们接下来将表演 两种不同组织来源的长寿祖细胞(LLPC)的代RNA测序和功能分析 以发现共享的和特定于组织的生存路径。这项研究的结果将揭示 负责人类体液免疫的PC亚群的全球种群结构并提供了对 个人电脑如何在地区性和系统性上控制感染。

Abstract: Plasma cells (PC) are responsible for maintaining serum antibody levels to pathogen. However, a comprehensive spatial map of PC subsets across tissue compartments in the human body is lacking. As a consequence, our understanding of global PC population structure across different tissues within individuals and also between different individuals is murky. Using unique and rare-to-access human tissue resources along with high-dimensional flow cytometry, will test the hypothesis that PC subset composition can be predicted by tissue site and that long-lived PC (LLPC) engage survival programs that are tailored to each site of origin. In Aim 1, we will identify known and novel PC subsets in lymphoid and mucosal tissues from normal human donors using complex flow cytometry and unbiased computational algorithms. We will integrate phenotype with signaling status and establish PC functional capabilities. In Aim 2, we will perform Next Generation RNA-Sequencing and functional assays on long-lived PCs (LLPC) derived from two distinct tissue sites in order to uncover shared versus tissue-specific survival pathways. Results from this study will reveal the global population structure of PC subsets responsible for human humoral immunity and provide insights into how PCs control infections regionally and systemically.