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：器官特定项目除营养吸收外，胃肠道对正常和其他器官系统的患病生理学，包括代谢，神经功能和免疫系统。肠道高分辨率的多模式3D地图将是无价的了解正常的肠功能和导致疾病的扰动的资源。我们的持续的目标是沿着小肠和结肠的长度创建此地图具有细微的功能地理专业。使用单核RNA+ATAC-SEQ，我们将同时介绍定义复合物的基因表达和调节程序驱动肠功能的细胞种群。我们将使用法典多重免疫测定定义这些细胞群体的空间关系，并使用串行创建3D地图部分。我们还将使用分子制图多路复用鱼测定转录本空间图更好地将单核数据集成到法典免疫图中。这些研究将以保存和采购的方式进行适用于高质量的分子图生成。我们的目标里程碑是描述六个总共有8个人口统计多样性的人的排便。生成越来越深的覆盖范围地图，将在光线覆盖范围内绘制两个肠地。 20个人。