Organ Specific Project

器官特定项目

基本信息

批准号：
10531083
负责人：
MICHAEL P. SNYDER
金额：
$ 156.45万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-23 至 2026-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10531083
关键词：
3-Dimensional ATAC-seq American Indians Antibodies Architecture Area Biological Assay Blood Vessels Brain Death COVID-19 testing Cell Nucleus Cells Chromatin Colon Communities Complex Confounding Factors (Epidemiology)Consent Consent Forms Data Data Set Disease Distal part of ileum Duodenum Enrollment Enterocytes Exhibits Fluorescent in Situ Hybridization Freezing Functional disorder Gastrointestinal tract structure Gene Expression Generations Genes Geography Goals Human Human BioMolecular Atlas Program Immune Immune system Immunoassay Individual Inflammatory Bowel Diseases Intestines Investigation Iron Lead Length Light Lymphatic Malignant Neoplasms Maps Metabolism Molecular Monitor Mucous Membrane Muscle Nerve Neurophysiology - biologic function Nuclear Nutrient Organ Organ Donor Organ Procurements Organ Transplantation Phase Physiological Physiology Policies Population Positioning Attribute Precision Health Production Protocols documentation RNA Resolution Resources Riboflavin Sampling Site Small Intestines South Dakota Standardization Structure Surface System Techniques Thiamine Thick Tissue Preservation Tissues Transcript Transplant Surgeon Vitamin B 12 Vitamin K Work bile salts body system cell type commensal microbes ethnic diversity human tissue improved lipidomics metabolomics microbiome multimodal data multimodality nutrient absorption programs reconstruction spatial relationship tissue mapping transcriptome transcriptome sequencing transcriptomics two-dimensional whole genome working group

项目摘要

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.

摘要：器官特定项目除了营养吸收之外，胃肠道对正常和消化系统也有广泛的影响。其他器官系统的患病生理机能，包括新陈代谢、神经功能和免疫系统。肠道的高分辨率、多模式 3D 地图将是非常宝贵的了解正常肠道功能和导致疾病的干扰的资源。我们的持续的目标是沿着小肠和结肠的长度创建这张图，这两者具有细致入微的地理专业化功能。使用单核RNA+ATAC-seq，我们将同时分析定义复杂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的空间关系并使用序列创建 3D 地图部分。我们还将使用分子制图多重 FISH 检测来生成转录物空间图，以更好地将单核数据整合到 CODEX 免疫图上。这些调查将对以某种方式保存和采购的组织进行适用于高质量分子图谱生成。我们的目标里程碑是表征六个总共 8 个人口结构不同的个体的肠道部位完全覆盖。生成在更多个体中绘制更深的覆盖图，将在光覆盖处绘制两个肠道位点 20人。