Harmonizing single cell and spatial transcriptomics across HuBMAP organs to generate reproducible and robust maps

协调 HuBMAP 器官的单细胞和空间转录组学，生成可重复且稳健的图谱

• 批准号: 10818848
• 负责人: GARRY P NOLAN
• 金额: $ 8.99万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 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/10818848
• 关键词: 3-Dimensional; ATAC-seq; Antibodies; Architecture; Area; Biological Assay; Biological Sciences; Blood Vessels; Cell Nucleus; Cells; Chromatin; Chromosome Mapping; Circulation; Collaborations; Collection; Colon; Communities; Complex; Consent; Data; Data Set; Deposition; Detection; Disease; Donor Selection; Educational workshop; Epithelium; Ethnic Origin; Exposure to; Fluorescent in Situ Hybridization; Food; Gene Expression; Gene Expression Regulation; Generations; Genes; Genome; Genomics; Heterogeneity; Homeostasis; Human; Human BioMolecular Atlas Program; Human body; Image; Imaging Techniques; Immune; Immunity; Immunoassay; Individual; Ingestion; Intestines; Length; Lymphatic; Maps; Mediating; Metabolism; Molecular; Mucous Membrane; Muscle; Neighborhoods; Neurophysiology - biologic function; North Dakota; Nucleic Acid Regulatory Sequences; Nutritional; Organ; Organ Donor; Organ Transplantation; Phase; Physiology; Play; Population; Postdoctoral Fellow; Preservation Technique; Process; Production; Protocols documentation; Regulator Genes; Reproducibility; Resolution; Resources; Role; Running; Sampling; Science; Signal Transduction; Site; Slide; Small Intestines; Small Nuclear RNA; South Dakota; Structure; Submucosa; Technology; Thick; Tissue Banks; Tissue Preservation; Tissue Sample; Tissue-Specific Gene Expression; Tissues; Training; Tribes; Underserved Population; Work; XCL1 gene; absorption; analysis pipeline; cell motility; cell type; cost; data sharing; data submission; genome wide association study; graduate student; indexing; insight; multimodal data; multimodality; multiparametric imaging; multiple omics; public repository; sex; single cell technology; single nucleus RNA-sequencing; tissue mapping; transcriptome; transcriptome sequencing; transcriptomics

PROJECT SUMMARY ABSTRACT: Overall The small bowel and colon are organs critical for maintaining homeostasis of the human body by mediating nutritional absorption upon the ingestion of food. Though both organs are extensive in length, there are known differences in function and cellular heterogeneity within different portions of each. Also, a cross section anywhere in the bowel reveals a complex layering of components involved in absorption and secretion, motility of gut contents, circulation, and immunity. In this submission, we propose to continue our efforts in the Stanford Tissue Mapping Center (TMC) to produce multi-modal, three-dimensional single-cell resolution maps of the small bowel and colonic wall structure. This will serve as a community resource to further study intestinal function and disease. We will collect tissues from deceased organ donors with explicit consent for distribution among the HuBMAP consortium and broad access genome data sharing (GDS). Three sets of technologies will then be employed. Tissue samples will be subjected to single-nuclei ATAC-seq and RNA-seq. These open chromatin and transcriptomic profiles will be spatially mapped to tissue sections using the CODEX (CO-Detection by indEXing) multiplexed spatial immunoassay. We will also employ the Molecular Cartography multiplexed fluorescence in situ hybridization (FISH) assay to enable more accurate integration of CODEX and single-nuclei data. The resultant three- dimensional maps will span all layers of the bowel wall and include the epithelial, enteroendocrine, vascular, lymphatic, nervous, immune, and muscular cell populations that contribute to normal bowel function.

摘要：总体而言