Core C: Human Thymus Core

核心C：人类胸腺核心

• 批准号: 10689280
• 负责人: Laura P. Hale
• 金额: $ 48.93万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10689280
• 关键词: Acceleration; Address; Adolescent; Adult; Age; Antigen-Presenting Cells; Architecture; Bioinformatics; Biology; Biostatistics Core; Board Certification; Cell Compartmentation; Cell Separation; Cells; Characteristics; Collection; Communities; Complement; Consultations; Critical Pathways; Cytoprotection; Data; Databases; Doctor of Philosophy; Ensure; Flow Cytometry; Foundations; Frozen Sections; Gene Expression; Gene Expression Profile; Generations; Goals; Growth; Hematopoietic; Heterogeneity; Histology; Homeostasis; Human; Immunophenotyping; Institution; Knowledge; Longevity; Mediating; Modernization; Molecular; Molecular Analysis; Monitor; Mus; Newborn Infant; Pathologist; Pathology; Pathway interactions; Perinatal; Population; Population Analysis; Procedures; Production; Quality Control; Records; Research; Research Personnel; Research Project Grants; Research Support; Resource Sharing; Resources; Scheme; Self Tolerance; Services; Signal Pathway; Sorting; Specific qualifier value; Standardization; Stromal Cells; T-Cell Receptor Genes; T-Lymphocyte; Thinking; Thymic Tissue; Thymic epithelial cell; Thymus Gland; Translations; Vaccines; Work; biobank; cell preparation; effector T cell; gene expression database; human tissue; innovation; molecular phenotype; mouse model; pathogen; phenotypic data; programs; service utilization; synergism; transcriptome sequencing; translational potential

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.

摘要 这一基于全面发现的P01的研究项目（RP）旨在确定具体的变化 在控制胸腺上皮细胞（TEC）、基质细胞和 胸腺造血抗原呈递细胞（HAPC）室动力学和谱系分级 从围产期胸腺扩张到幼年/成年体内平衡的过渡。RP的研究将侧重于 但是他们试图解决的问题需要小鼠和人类胸腺的比较 从围产期到幼年期的生物学变化。然而，人胸腺组织在 大多数机构和跨物种比较并不总是直截了当的。此外，强调 该P01关于解读TEC的大多数非重叠细胞亚群（RP 1，RP 2）中的异质性，其他 基质细胞（RP 2）和HAPC（RP 3）意味着可以潜在地获得与所有三种RP相关的数据 每一个人体组织的样本将这个集中的Human Thursday Core集成到P01中已经解决了 这些问题核心C服务将使RP 1-3能够解决有关翻译其 小鼠数据和以前未研究的人类胸腺生物学方面，通过三个重点具体 目的/服务任务：1）从健康捐赠者中获取和处理人类胸腺组织，以满足 项目特定的翻译需求; 2）TEC、其他基质细胞的富集和免疫表型分析， HAPC验证与RP 1-3中小鼠中鉴定的标志物类似的人等效标志物;和3） 通过产生标准化的、高质量的、可移植的、可移植的胸腺基质细胞和HAPC亚群的分子分析， 来自分选的人胸腺群体的受控单细胞（sc）和批量RNA-seq数据，用于核心分析 B。除了为RP提供关键服务外， 将由该核心产生的来自人胸腺的TEC、基质细胞和HAPC的子集将是一个 人类和小鼠胸腺研究社区重要的新资源。