Systematic dissection of gut cellular circuits [at single cell resolution]

肠道细胞回路的系统剖析[单细胞分辨率]

• 批准号: 9380153
• 负责人: Daniel Bartholomew Graham
• 金额: $ 179.6万
• 依托单位: BROAD INSTITUTE, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-01 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9380153
• 关键词: Address; Affect; Antigens; Atlases; Autoimmunity; Bacterial Infections; Binding; Biological Process; Biopsy; Cell Differentiation process; Cell Lineage; Cell physiology; Cells; Clinical; Collaborations; Communicable Diseases; Communication; Communities; Complex; Computational Biology; Computer Analysis; Data; Data Analyses; Diet; Dietary Factors; Disease; Dissection; Endocrine; Endocrine system; Enteral; Environment; Epithelial; Epithelial Cells; Epithelium; Evolution; Excision; Food Hypersensitivity; Gap Junctions; Gene Expression Profile; Genetic study; Genomic approach; Genomics; Health; Helminths; Hematopoietic; Homeostasis; Human; Human Activities; Immune response; Immunity; Immunology; Individual; Infection; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory disease of the intestine; Institutes; Intestines; Liquid substance; Malignant Neoplasms; Maps; Modeling; Molecular; Molecular Genetics; Mucosal Immunity; Mucous Membrane; Mus; Neurons; Nutrient; Organ; Pathologic; Pathology; Pathway interactions; Patients; Physiological; Positioning Attribute; Research Personnel; Resolution; Salmonella; Sampling; Series; Site; Small Intestines; Specimen; Stem cells; Symbiosis; System; T-Lymphocyte; Testing; Tissues; Validation; Work; body system; cell type; gastrointestinal epithelium; genetic manipulation; human disease; innovation; insight; intercellular communication; multi-scale modeling; novel; pathogen; response; transcriptome; uptake

ABSTRACT The gut serves as a nexus that connects and integrates organ systems throughout the body, with far-reaching consequences in health and disease. The biological function of the gut as an organ is the result of complex interactions between dynamic and heterogeneous cell types. Any pathological insult to the gut, such as barrier breach or infection, must be met with a response that is appropriate and proportional to the insult, such that homeostasis is re-established. In this application, we propose novel single-cell genomic approaches to decipher heterogeneous cellular responses to inflammatory challenge. Through a series of functional genetics studies, we aim to elucidate the molecular basis of mucosal immunity in the context of pathological inflammation. Towards this end, we propose the following specific aims: Aim 1. Comprehensively define all cell lineages and dynamic functional states in intestinal inflammation. Aim 2. Delineate intercellular communication networks that coordinate intestinal inflammation. Aim 3. Identify disease modifier pathways in human biopsies and integrate with intercellular communication networks.

摘要 肠道作为连接和整合整个身体器官系统的纽带，具有深远的意义。 健康和疾病的后果。肠道作为一个器官的生物学功能是复杂的 动态和异质细胞类型之间的相互作用。任何对肠道的病理性损伤，如屏障 违反或感染，必须得到适当的反应，并与侮辱成比例，这样， 体内平衡得以重建在这个应用中，我们提出了新的单细胞基因组方法， 解读对炎症刺激的异质细胞反应。通过一系列的功能遗传学 研究，我们的目的是阐明粘膜免疫的分子基础，在病理背景下， 炎症为此，我们提出以下具体目标： 目标1。全面定义肠道炎症中的所有细胞谱系和动态功能状态。 目标2.描绘协调肠道炎症的细胞间通讯网络。 目标3.识别人类活检中的疾病修饰通路并整合细胞间通讯 网络.