Core B - Biological Analysis

核心 B - 生物分析

• 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
• 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

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） 组织居住的免疫小球对与炎症相关的产生的贡献 秘书表型因素和对组织环境的影响尚不清楚，无法理解 在组织和器官特定环境中衰老和疾病中的免疫敏感。在这个项目中，一个潜水员团体 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建议的专家 耶鲁鼠组织映射中心免疫细胞感染（耶鲁-MTMC）通过研究 通过公正的单细胞分辨率OMICS方法定义的谱系标记的鼠标模型旨在发现 SASP产生细胞和新型生物标志物的细胞谱系，这些细胞定义基质和免疫细胞 体内感应。耶鲁-MTMC的生物分析核心（BAC）将产生细胞感应 - 相关的胸腺，骨髓，Sleen，PBMC和肠系膜脂肪组织的组织地图集。为了 检测并表征体内罕见的感觉细胞，构建Senscent的生物分子和细胞图 在免疫感应中实施的这些时机中的细胞，并剖析其对组织环境的影响， BAC将部署并结合三类生物分析管道，包括（i）2D和3D多路复用 成像（MI），（ii）转录组和蛋白质的单细胞分析（SCA），以及（iii）空间多词 测序（SMO），为了达到敏感性检测稀有感觉细胞的灵敏度，深度为表征 在基因组尺度上的感觉细胞的异质性，以及呼吸以绘制广泛的原位细胞 构建感觉细胞和相关组织微环境的地图。具体而言，BAC将 追求以下目的：（1）为谱系标记的小鼠分析的生物测量提供多个分析 通过与鼠组织映射合作的生物控制和感官模型的身份验证 中心。 （2）实施一系列的表征管道，以进行免疫的单细胞和空间幻象映射 细胞感应和组织环境，（3）通过增加这些管道来缩放和标准这些管道 测定速度和吞吐量在多重成像和空间多摩学测序中，并通过开发完全 集成和标准化的工作流程。耶鲁-MTMC的BAC带来了几种新型动物模型和独特的组织 将在Sennet中共享的标本以及新型的空间多摩学技术，这些技术将增强 财团的分析能力。它将产生一个多摩尼斯分子和细胞的senscent 多种淋巴机和非淋巴器官中的免疫细胞，并与人类Sennet团队合作以绘制 并确定跨组织和物种的常见感觉特征。