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Spatial and temporal mapping of cell fate within lymphoid tissue

淋巴组织内细胞命运的空间和时间图谱

基本信息

批准号：
10682561
负责人：
ELLEN A ROBEY
金额：
$ 64.77万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-11 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10682561
关键词：
3-Dimensional Anatomy Antibodies Area Bar Codes CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes Cell Surface Proteins Cell physiology Cells Cellular Indexing of Transcriptomes and Epitopes by Sequencing Communities Computational Biology Computer Analysis Computer software Computing Methodologies Data Development Engineering Environment Flow Cytometry Four-dimensional Gene Expression Profile Genes Genetically Engineered Mouse Genomics Immune Immune response Immune system Immunology Individual Infection Internet Lasers Location Lymphoid Tissue Maps Mature Thymocyte Measurement Membrane Proteins Messenger RNA Metadata Methods Microdissection Microscopy Molecular Names Pathway interactions Pattern Preparation Proteins RNA RNA analysis Regulatory T-Lymphocyte Research Research Personnel Resolution Resources Services Signal Transduction Slice Structure of thymic medulla Suspensions System T-Cell Development T-Lymphocyte Thymic Tissue Thymus Gland Time Tissues Wild Type Mouse cell type cohort computational pipelines imaging modality interdisciplinary approach interest laser capture microdissection mRNA Expression multiphoton imaging multiphoton microscopy new technology novel strategies optical imaging protein expression single cell analysis single-cell RNA sequencing temporal measurement thymocyte tool transcriptome user-friendly web portal

项目摘要

Summary: Spectacular recent advances in single cell genomics have provided high-resolution information about cell identity, however relating molecular information to the spatial and temporal context remains a major challenge. This is particularly relevant for the immune system, since immune responses occur in highly organized tissue environments, and involve tightly-controlled changes in cell state over time. Here we propose to develop new approaches to increase the spatial and temporal resolution of single cell analyses, and to use these methods to generate and then disseminate a 4-dimensional (time and 3D spatial coordinates) map of T cell development and the associated microenvironment in the thymus. In Aim 1, we will use simultaneous measurement of mRNA and surface proteins on single cells, together with computation and experimental approaches to develop a temporal map of cell state transitions during T cell development in the thymus. In Aim 2, we will use coherent Raman and multiphoton microscopy of living thymic tissue slices, together with laser microdissection, to isolate functionally relevant regions of tissues. We will then perform single cell analyses of individual cells within these defined regions and use computational analyses to define cell types and resolve cellular cross-talk. In Aim 3, we will increase the value of this resource to the scientific community, we will make the data readily accessible to researchers via a user-friendly interface. !

摘要：最近单细胞基因组学的惊人进展提供了高分辨率的信息