Core C: Experimental Models

项目摘要 Experimental Models Core负责管理、跟踪、质量控制和分发所有 胶质母细胞瘤（GBM）动物模型（患者来源的异种移植物（PDX）模型、PDX来源的类器官、同基因的 小鼠和基因工程小鼠）用于所有项目的实验研究和人类生物标本 在多个机构之间进行验证。核心还将负责从细胞中产生类器官。 这些模型，用于小鼠肿瘤的双光子体内成像，以及用于单细胞和空间转录组学， P01的技术资源。一套>180个PDX GBM模型和>5个同基因小鼠模型， 基因组分析（DNA、RNA测序）可用于项目的假设检验。人体标本 确认小鼠模型的发现将有助于验证性别差异，尽管不同性别之间的先天异质性 与小鼠模型相比，人类患者是一个警告。核心通过以下方式加强项目和P01： 协调用于实验研究的模型的分布，其中肿瘤细胞的性别是 通过性基因特异性PCR和性染色体核型分析进行鉴定。实验的目标 模型核心将通过以下具体目标来实现：1）创建、组织和维护 基础设施，然后部署同基因和基因工程小鼠胶质瘤模型， 异种移植GBM模型，短期GBM培养和类器官，提供高质量，科学相关的 使用标准化采集、质量控制、储存/跟踪和分发向P01研究者提供生物标本 根据批准的IACUC指南，以及2）制备高质量，科学相关的临床生物标本 通过在标准化收集、质量和安全方面的持续努力和创新， 控制（包括集中神经病理学审查）、储存/跟踪和在适当的人力下分发 受试者（OHRP）监管指南使用安全，易于访问的数据库。一个决定性的好处， 实验模型核心是所有项目中模型共享使用的协调和可见性， 共享质量控制、批次（或传代）效应、生长特征、基因组分析和交叉项目 实验结果的数据共享。

PROJECT SUMMARY The Experimental Models Core is responsible for curation, tracking, quality control, and distribution of all glioblastoma (GBM) animal models (patient-derived xenograft (PDX) models, PDX-derived organoids, syngeneic mouse and genetically engineered mice) for experimental studies in all Projects and biospecimens from humans for validation across multiple institutions. The Core will also be responsible for the generation of organoids from these models, for two-photon in vivo imaging of tumors in mice, and for single cell and spatial transcriptomics as technology resources for the P01. A suite of >180 PDX GBM models and >5 syngeneic mouse models with genomic profiling (DNA, RNA sequencing) are available for hypothesis testing by the projects. Human specimens to confirm findings from mouse models will help validate sex differences, albeit the innate heterogeneity across human patients compared to mouse models is a caveat. The core strengthens the projects and the P01 by coordinating the distribution of models for experimental studies in which the sex of the tumor cells are characterized via sex gene-specific PCR and sex chromosome karyotyping. The goals of the Experimental Models Core will be accomplished through the following specific aims: 1) To create, organize, and maintain infrastructure, then deploy syngeneic and genetically engineered mouse glioma models, patient-derived xenograft GBM models, short-term GBM cultures and organoids, providing high-quality, scientifically relevant biospecimens to P01 investigators using standardized collection, quality control, storage/tracking and distribution under approved IACUC guidelines, and 2) To make high-quality, scientifically-relevant clinical biospecimens available to the P01 investigators through continued efforts and innovations in standardized collection, quality control (including centralized neuro pathology review), storage/tracking and distribution under proper human subject (OHRP) regulatory guidelines using secure, readily accessible databases. A decided benefit of the Experimental Models Core is the coordination and visibility of shared use of models across all Projects, with shared quality control, batch (or passage) effects, growth characteristics, genomic profiling, and cross-Project data sharing from the experimental outcomes.