Molecular, Cellular, and Tissue Characterization Unit

项目摘要(定性股) 转移涉及癌细胞在原发肿瘤部位以外扩散的复杂过程， 也是大多数癌症死亡的原因。复杂性源于动态的相互作用 在异质和进化的癌细胞和肿瘤微环境之间，在 从局部浸润性癌症进展到转移性癌症。理解这一进程，这是 与免疫和发育密切相关，呼吁对各种细胞状态和 它们在进化过程中与当地生态位的互动。然而，构建这样一份地图集 由于缺乏对存在的所有细胞类型的先验知识，细胞状态构成了挑战 预期的单元格状态范围，或转换速率。为了克服这些挑战，我们提出了 三个迭代目标。首先，我们将建立一条坚固、经济高效、高质量的单电池管道 基因组学(主要是核糖体核糖核酸)鉴定临床样本，由生物医学研究所提供。 通过这项工作，我们将建立细胞类型、细胞状态和时间谱系追踪的分类 连接从原发肿瘤到转移的克隆。接下来，我们将建立一个强大的、成本- 提供高效、高质量的临床样本单细胞分辨率空间测绘流水线 生物质学家小组的目标是系统地绘制出 肿瘤/转移及其相关的微环境。最后，我们将评估和吸收 当这些新技术达到生产能力时，最好的新兴技术。这一点很重要，因为 单细胞技术领域正以惊人的速度向前发展，从而使 表征单位将保持对这些技术的最新了解。

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.