Core B - Biological Analysis

核心 B - 生物分析

基本信息

批准号：
10675115
负责人：
Rong Fan
金额：
$ 75.48万
依托单位：
YALE 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：
2022-08-02 至 2026-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10675115
关键词：
3-Dimensional Adipose tissue Aging Agreement Animal Model Area Atlases Biological Biological Assay Biological Markers Biology of Aging Biomedical Engineering Bone Marrow Breathing Categories Cell Aging Cell Lineage Cells Cellular Indexing of Transcriptomes and Epitopes by Sequencing Cellular biology Collaborations Computational Biology Cytometry Devices Disease Environment Evaluation Fluorescence Goals Hematopoietic Heterogeneity Human Image Immune Immune system Immunobiology In Situ Inflammation Inflammatory Investigation Iron Label Light Lymphoid Macrophage Maps Measures Mesentery Messenger RNA Microscopy Modality Modeling Molecular Motivation Mus Organ PTPRC gene Peripheral Blood Mononuclear Cell Phenotype Process Production Proteins RNA analysis Reporter Reproducibility Research Resolution Sampling Scanning Slide Sorting Specimen Speed Spleen Standardization Stromal Cells System Techniques Technology Thymic epithelial cell Thymus Gland Tissue atlas Tissues Training aged cell type exposed human population genome-wide in vivo interest molecular imaging mouse model multiple omics multiplexed imaging nano-string novel novel marker pathogen exposure senescence single cell analysis spatial integration synergism tissue mapping tool transcriptome

项目摘要

SUMMARY – Core B: Biological Analysis Core (BAC) The contribution of tissue-resident immune cells to the production of inflammatory senescence associated secretory phenotype factors and the impact on the tissue environment is unknown, precluding the understanding of immune senescence in aging and disease in tissue and organ specific context. In this project, a diverse group of experts in aging biology, immunobiology, bioengineering, cell biology, and computational biology propose a Yale murine Tissue Mapping Center for immune cell senescence (Yale-mTMC) through investigation of well- defined lineage-marked mouse models by unbiased single-cell resolution OMICS approaches aims to discover the cellular lineage of SASP producing cells and novel biomarkers that define stromal and immune-cell senescence in vivo. The Biological Analysis Core (BAC) of Yale-mTMC will create the cellular senescence- associated tissue atlases of thymus, bone marrow, spleen, PBMCs and mesenteric adipose tissue. In order to detect and characterize rare senescent cells in vivo, construct the biomolecular and cellular map of senescent cells in these tissues implicated in immune senescence, and dissect their impact on the tissue environment, the BAC will deploy and combine three categories of bioanalytical pipelines including (i) 2D and 3D Multiplexed Imaging (MI), (ii) Single Cell Analysis (SCA) of transcriptome and proteins, and (iii) Spatial Multi-Omics Sequencing (SMOS), in order to achieve the sensitivity to detect rare senescent cells, the depth to characterize the heterogeneity of senescent cells at the genome scale, and the breathe to map a wide range of cells in situ to construct the maps of senescent cells and the associated tissue microenvironments. Specifically, the BAC will pursue the following aims: (1) to provide biospecimens for analyses from lineage-marked mice with multiple biological controls and authentication of senescence-models through co-operation with murine Tissue Mapping Centers. (2) Implement an array of characterization pipelines for single-cell and spatial omics mapping of immune cell senescence and the tissue environment, and (3) to scale and standard these pipelines by increasing the assay speed and throughput in multiplex imaging and spatial multi-omics sequencing and by developing a fully integrated and standardized workflow. Yale-mTMC's BAC brings several novel animal models and unique tissue specimens that will be shared within SenNet as well as novel spatial multi-omics techniques that will enhance the analytical capability of the consortium. It will generate a multi-omics molecular and cell atlas of senescent immune cells in multiple lymphoid and non-lymphoid organs and collaborate with human SenNet teams to map and identify common senescent signatures across tissue and species.

摘要 – 核心 B：生物分析核心 (BAC) 组织驻留免疫细胞对相关炎症衰老产生的贡献分泌表型因素及其对组织环境的影响尚不清楚，妨碍了理解在这个项目中，不同的小组研究了衰老和疾病中免疫衰老在组织和器官特定背景下的研究。衰老生物学、免疫生物学、生物工程、细胞生物学和计算生物学专家的提案耶鲁大学小鼠免疫细胞衰老组织图谱中心 (Yale-mTMC) 通过对通过无偏单细胞分辨率 OMICS 方法定义谱系标记小鼠模型旨在发现 SASP 产生细胞的细胞谱系和定义基质细胞和免疫细胞的新型生物标志物 Yale-mTMC 的生物分析核心 (BAC) 将创建细胞衰老- 胸腺、骨髓、脾脏、PBMC 和肠系膜脂肪组织的相关组织图谱。检测和表征体内罕见的衰老细胞，构建衰老的生物分子和细胞图谱这些组织中与免疫衰老有关的细胞，并剖析它们对组织环境的影响， BAC 将部署和组合三类生物分析管道，包括 (i) 2D 和 3D 多重分析成像 (MI)、(ii) 转录组和蛋白质的单细胞分析 (SCA)，以及 (iii) 空间多组学测序（SMOS），以达到检测稀有衰老细胞的灵敏度，深度表征基因组范围内衰老细胞的异质性，以及原位绘制各种细胞的呼吸图具体而言，BAC 将构建衰老细胞和相关组织微环境的图谱。追求以下目标：（1）提供用于分析具有多种谱系标记的小鼠的生物样本通过与小鼠组织图谱合作进行生物控制和衰老模型验证 (2) 实施一系列用于免疫的单细胞和空间组学绘图的表征流程。细胞衰老和组织环境，以及（3）通过增加多重成像和空间多组学测序中的测定速度和通量，并通过开发完全 Yale-mTMC 的 BAC 带来了多种新颖的动物模型和独特的组织。将在 SenNet 内共享的样本以及新颖的空间多组学技术将增强该联盟的分析能力将生成衰老的多组学分子和细胞图谱。多个淋巴和非淋巴器官中的免疫细胞，并与人类 SenNet 团队合作绘制地图并识别跨组织和物种的常见衰老特征。