Core B - Biological Analysis

核心 B - 生物分析

• 批准号: 10553034
• 负责人: Rong Fan
• 金额: $ 97.46万
• 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/10553034
• 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; 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; 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; Research; Resolution; Sampling; Scanning; Slide; Specimen; Speed; Spleen; Standardization; Stromal Cells; System; Techniques; Technology; Thymic epithelial cell; Thymus Gland; Tissue atlas; Tissues; Training; aged; base; cell type; exposed human population; genome-wide; in vivo; interest; macrophage; molecular imaging; mouse model; multiple omics; multiplexed imaging; nano-string; novel; novel marker; operation; pathogen exposure; senescence; single cell analysis; 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) 组织驻留免疫细胞在炎性衰老相关过程中的作用 分泌表型因素及其对组织环境的影响尚不清楚，难以理解 衰老中的免疫衰老以及特定组织和器官背景下的疾病。在这个项目中，一个多元化的群体 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的专家提出了一种 耶鲁大学小鼠免疫细胞衰老组织图谱中心(YALE-mTMC)通过对Well-TMC的调查 通过无偏向单细胞分辨率OMICS方法建立明确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细胞和免疫细胞的新生物标记物 体内衰老。耶鲁-mTMC的生物分析核心(BAC)将产生细胞衰老- 胸腺、骨髓、脾、PBMC和肠系膜脂肪组织的相关组织图谱。为了 体内罕见衰老细胞的检测和鉴定，构建衰老的生物分子和细胞图谱 这些组织中的细胞与免疫衰老有关，并剖析了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多路复用 成像(MI)，(Ii)转录组和蛋白质的单细胞分析(SCA)，和(Iii)空间多组学 测序(SMOS)，为了达到检测罕见衰老细胞的灵敏度，对深度进行表征 衰老细胞在基因组水平上的异质性，以及呼吸以原位定位广泛的细胞 构建衰老细胞和相关组织微环境的图谱。具体地说，BAC将 追求以下目标：(1)为谱系标记的小鼠提供用于分析的生物谱系 通过与小鼠组织图谱合作进行衰老模型的生物学控制和验证 中锋。(2)实现了一组用于免疫单细胞和空间组学定位的特征流水线 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的分析速度和吞吐量，并通过开发完全的 一体化、标准化的工作流程。耶鲁-mTMC的BAC带来了几个新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。它将产生衰老的多组学分子和细胞图谱 多种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 并识别不同组织和物种的共同衰老特征。