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） 我们计划的一个中心焦点是了解特定细胞类型的作用，包括免疫细胞 在小鼠模型和人类中，PDAC在整个启动、发展和传播过程中对群体的影响。一 这项工作的一个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推移和对治疗的反应而变化。此外，虽然 每个项目都侧重于PDAC的不同方面，全面了解上皮细胞的作用， PDAC中的细胞区室和免疫系统将需要同时分析这些细胞类型中的每一种， 多种组织为了实现这些目标，我们将使用CO-Detection by indEXing（CODEX），一种新的方法 是由斯坦福大学的诺兰博士的研究小组产生的。CODEX将允许对组织切片进行细胞计数成像， 抗体。然后，来自该核心的CODEX数据可以与来自CyTOF和scRNA的互补数据相关联。 在单个项目中使用的Seq。核心C用于人类和小鼠胰腺研究的具体目的是： 1.为研究者提供CODEX处理，包括染色、成像和质量控制 2.提供CODEX分析，包括抗原聚类、细胞类型注释和邻域作图 3.与P01研究者协商，为CODEX开发新的抗体和试剂 4.合作开发组织采购、处理、储存和检索的标准工作流程 与人胰腺组织核心（核心B）。 项目1、2和3将专门使用CODEX核心平台进行小鼠和人体组织的研究。 核心C将与人体组织核心B密切合作，以确保适当的人体组织制备， 支持CODEX分析。因此，核心C将提供技术上困难的服务，并且在大多数情况下都不可用。 实验室，商业上无法获得或不可能在其他地方获得的材料，以及更可靠的服务 并且比在个体研究者的实验室中进行更具成本效益。CODEX核心 这在斯坦福大学将是一个全新的、独一无二的项目。