Core C: CODEX Core

核心 C：CODEX 核心

• 批准号: 10187130
• 负责人: GARRY P NOLAN
• 金额: $ 35.07万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10187130
• 关键词: Abbreviations; Algorithms; Antibodies; Antigens; Architecture; Biological Markers; Cell Communication; Cell Ontogeny; Cells; Cellular Structures; Cluster Analysis; Computing Methodologies; Consultations; Data; Detection; Development; Disease; Duct (organ) structure; Early Diagnosis; Ensure; Epithelial; Fibroblasts; Fluorescence-Activated Cell Sorting; Frequencies; Generations; Genetic; Goals; Graph; Human; Human Resources; Image; Immune; Immune Evasion; Immune system; Immunohistochemistry; Individual; Laboratories; Learning; Link; Malignant Neoplasms; Malignant neoplasm of pancreas; Maps; Mesenchymal; Metaplasia; Methods; Monitor; Mus; Neighborhoods; Pancreas; Pancreatic Ductal Adenocarcinoma; Population; Public Health; Quality Control; Reagent; Research; Research Personnel; Resources; Retrieval; Role; Services; Signal Transduction; Stains; Stereotyping; Time; Tissue Procurements; Tissue imaging; Tissues; Trees; Tumor Suppressor Genes; Tumor-associated macrophages; Ultrasonography; Visualization; Work; automated analysis; base; cancer cell; cancer therapy; cell type; chronic pancreatitis; computer program; cost; effective therapy; health goals; human tissue; immunoregulation; in vivo; indexing; mouse model; open source; pancreas imaging; pancreatic stellate cell; programs; response; single-cell RNA sequencing; spatial relationship; stem cells; tissue preparation; tool; treatment response; tumor; tumor growth; tumor microenvironment

ABSTRACT (Core C) A central focus of our program is understanding the roles of specific cell types, including immune cell populations, throughout the initiation, development and spread of PDAC in mouse models and in humans. A key aspect of this effort is to define the frequency, spatial relationships and activation states of cell types within tumors, and to learn how these parameters change over time and in response to therapy. Additionally, while each project focuses on a different aspect of PDAC, a comprehensive understanding of the role of the epithelial compartment and the immune system in PDAC will require simultaneous analysis of each of these cell types in multiple tissues. To achieve these goals, we will use CO-Detection by indEXing (CODEX), a new method generated by Dr. Nolan's group at Stanford. CODEX will allow cytometric imaging of tissue sections with dozens of antibodies. CODEX data from this Core can then be linked to complementary data from CyTOF and scRNA- Seq used in individual projects. The Specific Aims of Core C for human and mouse pancreas studies are: 1. Provide CODEX processing to investigators, including staining, imaging and quality control 2. Provide CODEX analysis, including antigen clustering, cell type annotation and neighborhood mapping 3. Develop new antibodies and reagents for CODEX in consultation with P01 investigators 4. Develop standard workflows for tissue procurement, processing, storage and retrieval in partnership with the human pancreas tissue core (Core B). Projects 1, 2 and 3 will specifically use the CODEX core platform for studies of both mouse and human tissues. Core C will work closely with the Human Tissue Core B to ensure appropriate human tissue preparation to support CODEX analysis. Thus, Core C will provide services technically difficult and not available in most laboratories, materials not available commercially or impossible to obtain elsewhere, and services more reliably and cost-effectively performed than if performed in an individual investigator's laboratory. This CODEX Core would be new, and unique at Stanford.

摘要（核心C） 我们程序的主要重点是了解特定细胞类型的作用，包括免疫细胞 PDAC在小鼠模型和人类中PDAC的整个启动，发展和传播过程中。一个 这项工作的关键方面是定义细胞类型的频率，空间关系和激活状态 肿瘤，并了解这些参数如何随着时间的流逝而变化并响应治疗。另外， 每个项目都侧重于PDAC的另一个方面，对上皮的作用有一个全面的理解 PDAC中的隔室和免疫系统将需要同时分析这些细胞类型 多个组织。为了实现这些目标，我们将通过索引（codex）使用共同检测，这是一种新方法 由斯坦福大学诺兰博士的小组生成。法典将允许数十个组织切片的细胞术成像 抗体。然后可以将来自该核心的法典数据链接到cytof和scrna-的互补数据 SEQ用于单个项目。核心C对人类和小鼠胰腺研究的具体目的是： 1。向调查人员提供法典处理，包括染色，成像和质量控制 2。提供法典分析，包括抗原聚类，细胞类型注释和邻居映射 3。与P01调查人员协商时开发新的抗体和试剂 4。开发用于组织采购，加工，存储和检索合作的标准工作流程 与人胰组织核心（核B）。 项目1、2和3将专门使用法典核心平台进行小鼠和人体组织的研究。 核C将与人体组织核心B紧密合作，以确保适当的人体组织准备 支持法典分析。因此，核心C将在技术上提供技术困难，并且在大多数中不可用 实验室，商业上无法获得的材料，无法获得其他地方，以及更可靠的服务 与在单个研究人员的实验室中进行的成本有效性能相比。此法典核心 将是新的，在斯坦福大学独特。