Organ Specific Project

摘要：器官专案 除了吸收营养外，胃肠道对正常和 其他器官系统的疾病生理学，包括新陈代谢、神经功能和 免疫系统。一张高分辨率、多模式的肠道3D地图将是一个无价的 了解正常的肠功能和导致疾病的扰动的资源。我们的 继续的目标是沿着小肠和结肠的长度创建这个地图，这两者都是 具有细微差别的功能地域专业化。使用单核RNA ATAC-SEQ，我们 将同时描述定义复合体的基因表达和调控程序 驱动肠道功能的细胞群。我们将使用Codex多重免疫分析来 定义这些细胞群体的空间关系并使用序列创建3D地图 横断面。我们还将使用分子地图多重FISH分析来生成 转录空间地图，以便更好地将单核数据与食典免疫地图相结合。 这些研究将在以某种方式保存和获取的组织上进行 适用于高质量的分子图谱生成。我们的目标里程碑是将六个 全覆盖范围内共有8个人口统计学上不同的个体的肠道部位。生成 更深层次的覆盖图在更多的人中，两个肠道部位将在光覆盖下绘制 20个人。

ABSTRACT: Organ Specific Project Beyond nutrient absorption, the gastrointestinal tract has wide-ranging effects on the normal and diseased physiologies of other organ systems, including metabolism, neural function, and the immune system. A high-resolution, multi-modal 3D map of the bowel would be an invaluable resource to understand normal bowel function and the perturbations that lead to disease. Our continued goal is to create this map along the length of the small bowel and colon, both of which have nuanced geographic specializations of function. Using single-nuclei RNA+ATAC-seq, we will simultaneously profile the gene expression and regulatory programs that define the complex cell populations that drive bowel function. We will use the CODEX multiplex immunoassay to define the spatial relationships of these cell populations and to create 3D maps using serial sections. We will also use the Molecular Cartography multiplex FISH assay to generate transcript spatial maps to better integrate the single-nuclei data to the CODEX immuno-maps. These investigations will be performed on tissues that are preserved and procured in a manner suitable for high-quality molecular map generation. Our target milestone is to characterize six bowel sites from a total of 8 demographically-diverse individuals at full coverage. To generate deeper coverage maps in more individuals, two bowel sites will be mapped at light coverage in 20 individuals.