Single-cell Mapping Center for Human Regulatory Elements and Gene Activity

人类调控元件和基因活性单细胞图谱中心

• 批准号: 10297718
• 负责人: Ansuman Satpathy
• 金额: $ 135.47万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10297718
• 关键词: Adopted; Adult; Age; Alzheimer' s Disease; Atlases; Autoimmune Diseases; Autoimmunity; Biological Assay; Bone Marrow Cells; COVID-19; Catalogs; Cell Lineage; Cell Surface Proteins; Cell surface; Cells; Chromatin; Communities; Computational Biology; Computing Methodologies; Consent; DNA; Data; Development; Disease; Elements; Functional disorder; Gene Expression; Generations; Genetic Transcription; Genome; Genomic approach; Genomics; Goals; Health; Homeostasis; Human; Human Development; Human Genetics; Immune; Immune system; Individual; Infection; Insulin-Dependent Diabetes Mellitus; Lesion; Life; Link; Malignant Neoplasms; Maps; Measurement; Metadata; Methods; Mission; Mitochondria; Multiple Sclerosis; Mutation; National Human Genome Research Institute; Nerve Degeneration; Neurodegenerative Disorders; Organ; Patients; Play; Proteins; Protocols documentation; Regulator Genes; Regulatory Element; Research; Research Personnel; Resolution; Resources; Role; Sampling; Site; Systemic Lupus Erythematosus; Techniques; Technology; Tissue Sample; Tissues; Work; biobank; body system; cell type; combinatorial; cost; cost efficient; data quality; data sharing; epigenome; epigenomics; experience; expression cloning; genetic variant; genome-wide; genome-wide analysis; genomic variation; healthy aging; high throughput technology; human disease; human tissue; indexing; individual patient; multimodality; multiple omics; peripheral blood; protein expression; single-cell RNA sequencing

PROJECT SUMMARY/ABSTRACT A comprehensive genome-wide map of DNA regulatory elements and gene expression in human cells is of critical importance for understanding how genomic variation impacts human health and disease. Since regulatory DNA elements are exceptionally cell type-, tissue-, and disease state-specific, a comprehensive catalog of these elements has been difficult to achieve. The overall mission of this IGVF Mapping Center is to create a high- quality, open-access, and single cell-resolution reference map of human regulatory elements and gene expression in immune cells during human development, across organ systems in healthy adults, and in tissues from diverse immune-related diseases. Our Mapping Center will leverage: (i) our recent advances in developing scalable and cost-efficient single-cell epigenome and multi-omic technologies to simultaneously map open chromatin sites, gene expression, intracellular and cell surface proteins, and clonal lineage tracing in each tissue sample, (ii) our prior technical improvements and application of these methods to primary tissues from humans, and (iii) our pre-existing human tissue biobank consisting of samples from more than 500 human individuals, 20 organ systems, and 15 disease conditions, consented for unrestricted access, genomic sequencing, and data sharing. In Specific Aim 1, we will work closely with the IGVF Consortium to establish cross-center plans for data generation, analyses, and effective coordination of sample access and sharing. In Specific Aim 2, we will generate a single-cell multi-omic atlas of immune cell types (and non-immune cells types, as determined with the IGVF) during development in early life, healthy aging, and across human organ systems. In Specific Aim 3, we will generate a single-cell multi-omic atlas in immune cell types from primary tissues in patients with autoimmunity, cancer, neurodegenerative disease, and infection. In Specific Aim 4, we will analyze regulatory sites and gene expression in the context of clonal differentiation trajectories inferred from mitochondrial lineage tracing and develop and maintain an integrated reference map of each datatype and tissue sample for the research community. Our Mapping Center, composed of 7 new investigators with extensive experience in single- cell genomic technologies and human disease analysis, will work closely with the IGVF to share technologies, resources, data, and tissue samples towards the shared goal of developing a comprehensive single-cell atlas of cell types, functional regulatory elements, and gene expression in humans.

项目总结/摘要 人类细胞中DNA调控元件和基因表达的全面基因组图谱是 这对于理解基因组变异如何影响人类健康和疾病至关重要。由于监管 DNA元件是异常的细胞类型，组织和疾病状态特异性，这些的全面目录 元素很难实现。该IGVF测绘中心的总体使命是创建一个高- 人类调控元件和基因的高质量、开放获取和单细胞分辨率参考图谱 在人类发育期间的免疫细胞中、在健康成人的器官系统中以及在组织中的表达 各种免疫相关疾病。我们的制图中心将利用：（i）我们最近在开发方面的进展 可扩展且具有成本效益的单细胞表观基因组和多组学技术， 染色质位点，基因表达，细胞内和细胞表面蛋白，以及每个组织中的克隆谱系追踪 样本，（ii）我们之前的技术改进以及这些方法在人类初级组织中的应用， 和（iii）我们现有的人体组织生物库，包括来自500多个人类个体的样本，20 器官系统和15种疾病，同意不受限制地访问，基因组测序和数据 共享在具体目标1中，我们将与IGVF联盟密切合作，建立跨中心的数据计划 生成、分析和有效协调样本访问和共享。在第二阶段，我们将 生成免疫细胞类型（和非免疫细胞类型，如用免疫细胞测定的）的单细胞多组学图谱。 IGVF）在生命早期发育、健康老龄化和跨越人体器官系统的过程中。在具体目标3中， 我们将从患有以下疾病的患者的原代组织中生成免疫细胞类型的单细胞多组图谱： 自身免疫、癌症、神经变性疾病和感染。在具体目标4中，我们将分析监管 从线粒体谱系推断克隆分化轨迹的位点和基因表达 追踪、开发和维护每个数据类型和组织样本的综合参考图， 研究社区。我们的测绘中心，由7名新的调查员组成，他们在单一领域拥有丰富的经验， 细胞基因组技术和人类疾病分析，将与IGVF密切合作，分享技术， 资源，数据和组织样本，以实现开发一个全面的单细胞图谱的共同目标。 人类的细胞类型、功能调节元件和基因表达。