Core C: Biological Analysis Core

核心C：生物分析核心

• 批准号: 10384403
• 负责人: Rong Fan
• 金额: $ 50.66万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10384403
• 关键词: Core; Biological; Analysis

PROJECT SUMMARY – Core C (Biological Analysis Core) Cellular senescence in human primary lymphoid organs such as bone marrow (BM) and thymus, and secondary lymphoid organs such as tonsil and lymph nodes (LNs) have been reported to show complex roles in normal hematopoiesis, immune function, aging, and disease development. These organs are among the most active, dynamic, and plastic physiologic systems. How cellular senescence is associated with stress- induced or age-related functional impairment, what types or subtypes of senescent cells are present and their spatial heterogeneity in the lymphoid tissues and how these cells impact the tissue environments remain poorly understood, precluding the development of strategies to target these cells to improve healthspan/lifespan or harnessing these cells or secreted factors to promote tissue remodeling and repair. Yale TMC Core C: Biological Analysis Core (BAC) will deploy a suite of high-resolution, high-content and high-throughput single- cell & spatial omics technologies to construct comprehensive maps of cellular senescence and the associated environments in primary human cells and human lymphoid tissues. Four major biological analyses will be performed: single-cell high-plex protein secretome profiling, single-cell proteo-transcriptomic sequencing (scCITE-seq), spatial proteo-transcriptomic sequencing at cellular level (DBiT-seq), and spatial molecular imaging (SMI) at single molecule resolution. Specifically, we will conduct (1) single-cell protein secretome profiling of SAPS heterogeneity using induced senescent cell models and body fluids, (2) single-cell and spatial proteo-transcriptomic sequencing to map senescent cells and environments in human lymphoid tissues. (3) high-plex proteo-transcriptomic spatial molecular imaging of lymphoid tissues. We envision that the proposed project will generate extensive multiscale, multimodality, and multifaceted data to characterize phenotypic, functional and spatial heterogeneity of senescent cells in response to multiple inducers or modifiers, identify biomarkers of senescent cell subtypes and neighborhoods, and construct maps and atlases of cellular senescence and environments in primary and secondary lymphoid organs of humans over longitudinal time frames, representing a highly valuable resource for a wide range of biomedical research.

项目摘要 - 核心C（生物分析核心） 人类原发性淋巴机构中的细胞感应，例如骨髓（BM）和胸腺，以及 据报道，次要淋巴机构（如扁桃体和淋巴结（LNS））已显示出复杂的作用 在正常的造血，免疫功能，衰老和疾病发展。这些器官是 最活跃，动态和塑料生理系统。细胞感应如何与应力相关 诱导或与年龄相关的功能障碍，存在什么类型或亚型的感觉细胞，它们 淋巴组织中的空间异质性以及这些细胞如何影响组织环境保持较差 理解，排除针对这些细胞的策略的制定，以改善健康范围/寿命或 利用这些细胞或分泌因素促进组织重塑和修复。耶鲁TMC核心C： 生物分析核心（BAC）将部署一套高分辨率，高通量和高通量单一的套件 细胞和空间法技术构建细胞感应的综合图和相关的综合图 原代人细胞和人淋巴组织中的环境。四个主要的生物学分析将是 进行：单细胞高质子蛋白分泌组谱分析，单细胞蛋白转录测序 （sccite-seq），在细胞水平（DBIT-SEQ）和空间分子处的空间蛋白转录测序 单分子分辨率的成像（SMI）。具体而言，我们将进行（1）单细胞蛋白分泌组 使用诱导的感觉细胞模型和体液对SAPS异质性进行分析，（2）单细胞和空间 蛋白转录组测序以绘制人淋巴组织中的感觉细胞和环境。 （3） 淋巴组织的高质子蛋白转录组合分子成像。我们设想提出的 项目将生成广泛的多尺度，多模式和多面数据，以表征表型， 响应多个诱导剂或修饰符的感觉细胞的功能和空间异质性，识别 感觉细胞亚型和邻域的生物标志物，以及构造细胞的地图和地图集 纵向时间的一级和继发性淋巴机器人的感应和环境 框架，代表了广泛的生物医学研究的高度宝贵资源。