Core2: Transcriptomics and Chromatin Structure

基因组和染色质分析核心(核心B)：摘要 基因组和染色质分析核心(核心B)将协作向项目1和项目2提供服务 核心A，重点是血管内应激和血管内应激诱导的转录模式变化的作用 外渗对血管外存活、休眠和生长的影响。GCC将负责分析 受肿瘤细胞血管和移行影响的转录和染色质事件 隔离在项目1和2中的过程。GCC将部署最先进的技术，包括单细胞核糖核酸 测序、基因组图谱(例如，Hi-C)以及染色质结构和分子的纳米级成像 状态，这些结果将被用于力学属性和信号的计算建模 参与机械适应和染色质扰动的途径(核心A)。 在血液中和渗出过程中，肿瘤细胞暴露在各种物理应激源中， 包括剪切应力造成的机械损伤和穿过狭窄的毛细血管 核变形。目前还不能完全理解机械应力和由此产生的染色质错乱是如何 转录改变影响肿瘤细胞形成转移的能力，导致侵袭性疾病， 发展休眠，培养其整体生存能力。 核心B将提供基因组和染色质分析，使项目能够开始解决这些问题 关于机械适应在转移中的后果的长期问题。核心B将利用单一- 用于转录分析和基因组图谱绘制的细胞信使核糖核酸测序(Hi-C或Low-C) Input Hi-C)和一套独特的纳米级成像技术(3-D染色质扫描透射式电子 用于染色质的层析成像、光学单分子纳米显微镜和光学光谱纳米传感 对项目中模型系统生成的细胞进行构象分析。此外，数据上的 将向Core提供染色质结构，包括基因组图谱和染色质构象成像 能够对转移的肿瘤细胞的机械和表型特性进行建模。超越了 U54中心的范围和项目完成后，转录重新编程的正常化 可能被探索用于肿瘤转移的靶向治疗。

Genomic and Chromatin Analysis Core (Core B): SUMMARY The Genomic and Chromatin Analysis Core (Core B) will provide services to Projects 1 and 2, in collaboration with Core A, focusing on the role of alterations in transcriptional patterns induced by intravascular stress and extravasation on extravascular survival, dormancy, and outgrowth. GCC will be responsible for analyzing transcriptional and chromatin events that are affected by and may affect tumor cell vascular and transmigration processes isolated in Projects 1 and 2. GCC will deploy state-of-the-art technologies, including single-cell mRNA sequencing, genome mapping (e.g., Hi-C), and the nanoscale imaging of chromatin structural and molecular states, and these results will be used for computational modeling of the mechanical properties and the signaling pathways involved in mechano-adaptation and chromatin perturbation (Core A). In the bloodstream and during extravasation, tumor cells are exposed to a variety of physical stressors, including mechanical damage due to shear stress and passage through narrow capillaries with substantial nuclear deformations. It is not fully understood how mechanical stress and the resulting chromatin derangement and transcriptional alterations affect the ability of tumor cells to form metastases, lead to aggressive disease, develop dormancy, and foster their overall survival ability. Core B will provide genomic and chromatin analyses that will enable the Projects to begin addressing these long-standing questions on the consequences of mechano-adaptation in metastasis. Core B will leverage single- cell mRNA sequencing for transcription analysis as well as genome mapping (Hi-C, whenever possible, or Low- input Hi-C) and a unique suite of nanoscale imaging technologies (3-D chromatin scanning transmission electron tomography, optical single-molecule nanoscopy, and optical spectroscopic nanosensing) for chromatin conformation analysis on cells generated by the model systems in the Projects. Furthermore, the data on chromatin structure, including genome mapping and chromatin conformation imaging, will be provided to Core A to enable the modeling of the mechanical and phenotypic properties of metastasizing tumor cells. Beyond the scope of the U54 Center and upon completion of the Projects, the normalization of transcriptional reprogramming might be explored for therapeutic targeting of metastasis.