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.

总结-核心B：生物分析核心（BAC） 组织驻留免疫细胞对炎症性衰老相关的产生的贡献 分泌表型因子和对组织环境的影响是未知的，排除了理解 免疫衰老和组织器官特异性疾病。在这个项目中， 衰老生物学、免疫生物学、生物工程学、细胞生物学和计算生物学的专家提出了一个 耶鲁大学免疫细胞衰老组织图谱中心（Yale-mTMC）通过研究 通过无偏单细胞分辨率OMICS方法定义的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和免疫细胞的新生物标志物 体内衰老耶鲁mTMC的生物分析核心（BAC）将创造细胞衰老- 胸腺、骨髓、脾脏、PBMC和肠系膜脂肪组织的相关组织图谱。为了 检测和表征体内罕见的衰老细胞，构建衰老细胞的生物分子和细胞图谱， 这些组织中的细胞参与免疫衰老，并剖析它们对组织环境的影响， BAC将部署和联合收割机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）空间多组学 测序（SMOS），以实现检测罕见衰老细胞的灵敏度，表征的深度 衰老细胞在基因组尺度上的异质性，以及原位绘制大范围细胞的呼吸 构建衰老细胞和相关组织微环境的图谱。具体而言，BAC将 追求以下目标：（1）提供用于分析的来自谱系标记小鼠的生物标本， 通过与小鼠组织图谱合作进行衰老模型的生物学控制和鉴定 中心. (2)实施一系列表征管道，用于免疫细胞的单细胞和空间组学映射 细胞衰老和组织环境，以及（3）通过增加 分析速度和通量的多重成像和空间多组学测序，并通过开发一个全面的 集成和标准化的工作流程。耶鲁mTMC的BAC带来了几种新颖的动物模型和独特的组织 将在SenNet内共享的标本以及将增强 财团的分析能力。它将产生一个多组学的分子和细胞图谱的衰老 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， 并识别组织和物种中常见的衰老特征。