Core C: Biological Analysis Core

项目总结-核心C（生物学分析核心） 人初级淋巴器官如骨髓（BM）和胸腺中的细胞衰老，以及 次级淋巴器官如扁桃体和淋巴结（LN）已被报道显示出复杂的作用 在正常造血、免疫功能、衰老和疾病发展中的作用。这些器官属于 最活跃、动态和可塑性的生理系统。细胞衰老与压力的关系- 诱导或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，排除了针对这些细胞以改善健康寿命/寿命的策略的发展， 利用这些细胞或分泌的因子来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，高内容和高通量的单- 细胞和空间组学技术构建细胞衰老和相关的综合地图 在原代人类细胞和人类淋巴组织中的环境中。四个主要的生物学分析将是 进行：单细胞高重蛋白分泌组分析，单细胞蛋白质转录组测序 在细胞水平上的空间蛋白质转录组测序（DBiT-seq）和空间分子生物学测序（SCCITE-seq）。 成像（SMI）在单分子分辨率。具体来说，我们将进行（1）单细胞蛋白分泌组 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，以绘制人类淋巴组织中的衰老细胞和环境。（三） 淋巴组织的高重蛋白质-转录组空间分子成像。我们设想， 该项目将产生广泛的多尺度，多模态和多方面的数据，以表征表型， 衰老细胞对多种诱导剂或修饰剂反应的功能和空间异质性， 衰老细胞亚型和邻居的生物标志物，并构建细胞的地图和地图集。 人类初级和次级淋巴器官的衰老和环境随时间的变化 框架，代表了一个非常宝贵的资源，为广泛的生物医学研究。

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.