Organ Specific Project

摘要：器官特异性项目 除了营养吸收之外，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， 免疫系统一个高分辨率，多模式的肠道3D地图将是一个非常宝贵的 了解正常肠道功能和导致疾病的扰动的资源。我们 我们的目标是沿着小肠和结肠的长度沿着创建这个地图，这两个地图都 在功能上有着细微的地理分工。使用单核RNA+ATAC-seq，我们 将同时分析基因表达和定义复合物的调控程序， 驱动肠道功能的细胞群。我们将使用CODEX多重免疫测定， 定义这些细胞群的空间关系，并使用序列 路段我们还将使用分子制图多重FISH测定来生成 转录物空间图，以更好地将单核数据整合到CODEX免疫图中。 这些研究将在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描述六个 在完全覆盖下，来自总共8个人口统计学上不同的个体的肠道部位。完成网站 在更多的个体中绘制更深的覆盖范围， 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.