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.

项目概要（特性描述股） 转移涉及癌细胞扩散到原发肿瘤部位以外的复杂过程， 也是大多数癌症死亡的原因。复杂性来自于一种动态的相互作用 异质性和进化中的癌细胞与肿瘤微环境之间的关系， 从局部浸润性发展为转移性癌症。理解这个过程， 与免疫和发育密切相关，需要表征各种细胞状态， 他们在发展过程中与当地生态位的相互作用。然而，构建这样一个地图集， 由于缺乏所有存在的细胞类型的先验知识， 预期的细胞状态范围，或转换速率。为了克服这些挑战，我们建议 三个迭代目标。首先，我们将建立一个强大的，具有成本效益的，高品质的管道，为单细胞 生物样本部门提供的临床样本的基因组学（主要是RNA）表征。 通过这项工作，我们将建立一个分类的细胞类型，细胞状态和时间谱系跟踪 连接原发肿瘤和转移肿瘤的克隆。接下来，我们将建立一个强大的，成本- 为临床样本的单细胞分辨率空间映射提供了有效、高质量的管道 由生物标本股进行，目标是系统地绘制 肿瘤/转移及其相关微环境。最后，我们将评估和吸收 最好的新兴技术，因为这些达到生产水平的能力。这是很重要的， 单细胞技术领域正以惊人的速度向前发展，从而平衡了 表征单位将继续对这些技术的最新。