Molecular, Cellular, and Tissue Characterization Unit

分子、细胞和组织表征单元

• 批准号: 10249192
• 负责人: Dana Pe'er
• 金额: $ 100.84万
• 依托单位: SLOAN-KETTERING INST CAN RESEARCH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249192
• 关键词: Address; Anatomy; Antibodies; Atlases; Autopsy; Biology; Biopsy; Calibration; Cells; Cessation of life; Clinical; Complex; Copy Number Polymorphism; DNA; Data; Development; Disseminated Malignant Neoplasm; Dissociation; Distant Metastasis; Emerging Technologies; Event; Excision; Freezing; Gene Expression Profiling; Generations; Genomics; Goals; Growth; Histology; Human; Human body; Image; Imaging technology; Immune system; Immunity; Knowledge; Lesion; Link; Liver; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Malignant neoplasm of pancreas; Maps; Metastatic Neoplasm to the Central Nervous System; Metastatic malignant neoplasm to brain; Metastatic to; Molecular; Neoplasm Metastasis; Pancreas; Patients; Peritoneum; Phylogeny; Primary Neoplasm; Process; Production; Proteins; Protocols documentation; RNA; Resolution; Sampling; Site; Small Nuclear RNA; Source; Structure; Taxonomy; Technical Expertise; Technology; Tissue Sample; Tissues; X-Ray Computed Tomography; base; cancer cell; cell type; cost effective; insight; multiple omics; programs; single cell technology; single-cell RNA sequencing; standard of care; temporal measurement; therapeutic target; tumor; tumor microenvironment

PROJECT SUMMARY (Characterization Unit) Metastasis involves the complex process of spreading of cancer cells beyond the primary tumor site, and is the cause of the majority of cancer deaths. The complexity arises from a dynamic interplay between heterogeneous and evolving cancer cells and the tumor microenvironment, during the progression from locally invasive to metastatic cancer. Understanding this progression, which is closely linked to immunity and development, calls for characterization of the various cell states and their interaction with the local niche during the progression. However, constructing such an atlas of the cellular states poses challenges due to the lack of a priori knowledge of all cell types present, the range of cell states to expect, or the rates of transition. To overcome these challenges we propose three iterative aims. First, we will establish a robust, cost-effective, high quality pipeline for single-cell genomics (primarily RNA) characterization of clinical samples provided by the Biospecimen Unit. Through this effort we will build a taxonomy of cell types, cell states and temporal lineage tracing connecting clones from the primary tumor to metastasis. Next, we will establish a robust, cost- effective, high quality pipeline for spatial mapping at single-cell resolution of clinical samples provided by the Biospecimen Unit with the goal systematically mapping the spatial structure of tumors/metastasis and their associated microenvironment. Finally, we will evaluate and assimilate the best new emerging technologies as these reach production level capacity. This is important to do as the field of single-cell technologies is moving forward at a staggering pace, thus poising the characterization unit will remain up to date on these technologies.

项目摘要（表征单元） 转移涉及在原发性肿瘤部位以外的癌细胞扩散的复杂过程， 这是大多数癌症死亡的原因。复杂性来自动态相互作用 在异质和不断发展的癌细胞与肿瘤微环境之间 从局部侵入性转向转移性癌症的发展。了解这一进展，那就是 与免疫力和发展密切相关，呼吁对各种细胞状态进行表征以及 他们在进展过程中与当地利基市场的相互作用。但是，建造这样的地图集 由于缺乏所有细胞类型的先验知识，蜂窝状态构成了挑战 细胞状态期望的范围或过渡速率。为了克服这些挑战，我们提出 三个迭代目标。首先，我们将为单细胞建立强大的，成本效益的高质量管道 基因组学（主要是RNA）表征生物测量单元提供的临床样本。 通过这项努力，我们将建立细胞类型，细胞状态和时间谱系跟踪的分类法 将克隆从原发性肿瘤连接到转移。接下来，我们将建立一个强大的成本 - 在提供的临床样品单细胞分辨率下，有效的高质量管道用于空间映射 由生物循环单元具有系统地绘制的空间结构 肿瘤/转移及其相关的微环境。最后，我们将评估和同化 最佳新的新兴技术，因为这些技术达到了生产水平。这很重要 单细胞技术领域正在以惊人的速度前进，从而使 这些技术将保持最新状态。