Core C: Human Thymus Core

摘要 这个以发现为基础的综合性P01的研究项目(RP)试图确定具体的变化 在转录谱和信号通路中控制胸腺上皮细胞(TEC)、基质细胞和 胸腺造血抗原提呈细胞(HAPC)的隔室动力学和谱系 从围产期胸腺扩张到幼年/成年胸腺内稳态的过渡。RPS中的研究将集中在 小鼠的模型，但他们试图解决的问题需要比较小鼠和人类的胸腺 从围产期到青少年的生物学转变。然而，人类胸腺组织在以下位置并不容易获得 大多数机构和跨物种比较并不总是直截了当的。此外，强调的是 本P01关于破译TECs(RP1，RP2)的主要非重叠细胞亚群的异质性，其他 基质细胞(RP2)和HAPC(RP3)意味着可以潜在地获得与所有三个RP相关的数据 从每一个被研究的人体组织中。将这种集中的人类胸腺核心整合到P01中的问题已经解决 这些问题。核心C服务将允许RP 1-3解决有关其翻译的知识差距 小鼠数据和以前未曾研究过的人类胸腺生物学方面，通过三个特定的焦点 目标/服务任务：1)从健康捐赠者那里采购和加工人胸腺组织，以满足 特定于项目的翻译需求；2)TEC、其他基质细胞的浓缩和免疫表型；以及 HAPC验证人类等值标记，类似于在RP 1-3中在小鼠中识别的标记；以及3) 胸腺基质细胞和HAPC亚群的分子分析通过产生标准化的，高质量的 用于Core分析的受控单细胞(Sc)和来自分选的人胸腺群体的批量RNA-seq数据 B.除了为RPS提供关键服务外，基因表达的综合数据库 这个核心将产生来自人类胸腺的TEC、基质细胞和HAPC的子集 为人类和小鼠胸腺研究社区提供了重要的新资源。

Abstract The Research Projects (RP) of this comprehensive discovery-based P01 seek to identify specific changes in the transcriptional profiles and signaling pathways that control thymic epithelial cell (TEC), stromal cell, and thymic hematopoietic antigen presenting cell (HAPC) compartment dynamics and lineage hierarchies during the transition from perinatal thymus expansion to juvenile/adult homeostasis. Studies in the RPs will focus on murine models, but the questions they seek to address require comparison of mouse and human thymus biology across the perinatal to juvenile transition. However, human thymus tissue is not readily available at most institutions and cross-species comparisons are not always straight-forward. In addition, the emphasis of this P01 on deciphering heterogeneity in mostly non-overlapping cellular subsets of TECs (RP1, RP2), other stromal cells, (RP2), and HAPCs (RP3) mean that data relevant to all three RPs can potentially be obtained from each human tissue studied. Integration of this centralized Human Thymus Core into the P01 has resolved these issues. Core C services will allow RP 1-3 to address the knowledge gaps regarding translation of their mouse data and previously unstudied aspects of human thymus biology, via three focused specific aims/Service Tasks: 1) Procurement and processing of human thymus tissues from healthy donors to meet project-specific translation needs; 2) Enrichment and immunophenotyping of TECs, other stromal cells, and HAPCs to validate human equivalent markers analogous to those identified in mice in RP 1-3; and 3) Molecular analysis of thymic stromal cells and HAPC subsets through generation of standardized, quality- controlled single cell (sc) and bulk RNA-seq data from sorted human thymus populations for analysis by Core B. In addition to providing critical services to the RPs, the comprehensive database of gene expression in subsets of TEC, stromal cells, and HAPCs from human thymus that will be generated by this Core will be a significant new resource for both human and mouse thymus research communities.