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） 人类初级淋巴器官（例如骨髓（BM）和胸腺）的细胞衰老，以及 据报道，扁桃体和淋巴结 (LN) 等次级淋巴器官具有复杂的作用 这些器官都参与正常的造血、免疫功能、衰老和疾病的发展。 最活跃、动态和可塑的生理系统。细胞衰老如何与压力相关。 诱导的或与年龄相关的功能障碍，存在哪些类型或亚型的衰老细胞及其 淋巴组织的空间异质性以及这些细胞如何影响组织环境仍然很差 理解，妨碍制定针对这些细胞的策略以改善健康/寿命或 利用这些细胞或分泌因子促进组织重塑和修复 Yale TMC Core C： 生物分析核心（BAC）将部署一套高分辨率、高内涵和高通量的单 细胞和空间组学技术构建细胞衰老及相关的综合图谱 人类原代细胞和人类淋巴组织的环境将进行四项主要的生物学分析。 进行：单细胞高复合蛋白分泌组分析、单细胞蛋白质转录组测序 (scCITE-seq)、细胞水平的空间蛋白质转录组测序 (DBiT-seq) 和空间分子 具体来说，我们将进行（1）单细胞蛋白质分泌组成像（SMI）。 使用诱导衰老细胞模型和体液分析 SAPS 异质性，(2) 单细胞和空间 蛋白质转录组测序可绘制人类淋巴组织中的衰老细胞和环境图谱 (3)。 我们设想所提出的淋巴组织的高复数蛋白质转录组空间分子成像。 该项目将产生广泛的多尺度、多模态和多方面的数据来表征表型、 衰老细胞响应多种诱导剂或调节剂的功能和空间异质性，识别 衰老细胞亚型和邻域的生物标志物，并构建细胞图谱和图谱 人类初级和次级淋巴器官随纵向时间的衰老和环境 框架，代表了广泛的生物医学研究的非常有价值的资源。