Senescent cell mapping, identification and validation for human somatic and reproductive tissues

人类体细胞和生殖组织的衰老细胞图谱、鉴定和验证

• 批准号: 10376495
• 负责人: Judith Campisi
• 金额: $ 270万
• 依托单位: BUCK INSTITUTE FOR RESEARCH ON AGING
• 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/10376495
• 关键词: Advanced Development; Affect; Age; Aging; Atlases; Biocompatible Materials; Biologic Characteristic; Biological; Biological Markers; Biomedical Research; Breast; Budgets; Cell Aging; Cell Proliferation; Cells; Characteristics; Collaborations; Communities; Complement; Complex; Data; Data Analyses; Data Coordinating Center; Development; Distal; Ensure; Epithelial; Feedback; Follicular Fluid; Gene Expression Profile; Genetic; Goals; Growth Factor; Head; Health; Human; Individual; Institutes; Laboratories; Lipids; Malignant Neoplasms; Maps; Mass Spectrum Analysis; Molecular; Molecular Analysis; Mus; Nerve Degeneration; Organism; Output; Ovary; Participant; Pathologic Processes; Pathology; Peptide Hydrolases; Pharmacology; Phenotype; Physiological Processes; Physiology; Plasma; Play; Principal Investigator; Process; Proteome; Proteomics; Protocols documentation; Research; Research Personnel; Resource Sharing; Resources; Role; Sampling; Scientist; Skeletal Muscle; Specimen; Structure; Techniques; Technology; Time; Tissues; Urine; Validation; age related; base; biobank; cell type; chemokine; cytokine; data sharing; design; experience; human tissue; improved; interest; method development; new technology; phenotypic biomarker; reproductive; response; senescence; single cell technology; stressor; technology development; transcriptome; transcriptomics; web site

OVERALL TMC - PROJECT SUMMARY Cellular senescence is a multi-faceted cell fate that arrests cell proliferation and activates the synthesis and secretion of numerous cytokines, chemokines, growth factors, proteases and lipids, termed the Senescence Associated Secretory Phenotype (SASP). The SASP can influence tissue microenvironments, locally and distally, and thus senescent cells can strongly affect tissue function. Senescent cells (SnCs) increase with age in most vertebrate organisms, including mice and humans, and it is increasingly clear through both genetic and pharmacological manipulations that they can drive a growing list of age-related pathologies, ranging from neurodegeneration to cancer. At present, there are no invariant biomarkers of SnCs and the molecular characteristics of SnCs are remarkably heterogeneous and variable, depending on cell and tissue type, microenvironment, senescence inducer, and timing. Our overall goal is to determine, molecularly and spatially, when and where senescent cells occur in humans, and also how their patterns of gene expression and SASPs vary with tissue physiology and age. These goals are also the goals of the SenNet Consortium. We therefore propose to establish a SenNet tissue mapping center (TMC) comprised of an Administrative Core, Biospecimen Core, Biological Analysis Core and Data Analysis Core. Our proposed TMC will focus on three human tissues (ovary, breast and skeletal muscle) and three biofluids (follicular fluid, plasma and urine). These samples have distinct biological characteristics and cell types (somatic and reproductive; stromal, epithelial and vasculature) that show significant changes with age. All materials are available through established collaborations, subcontractors and/or biobanks (through the Biospecimen Core). Their analyses will include cutting-edge transcriptomic and proteomic techniques that will take advantage of the expertise of several Buck Institute investigators. Our preliminary data show that these tissues and biofluids are amenable to the state-of-the-art technologies proposed in the Biological Analysis and Data Analysis Cores, as well as new technologies proposed in our accompanying Technology Development application (RFA-RM- 21-009). Importantly, our findings will be applicable to many other human tissues and biofluids in order to encompass and complement the overall goals of the larger SenNet Consortium. The Administrative Core will coordinate all aspects of the TMC, from specimen acquisition to analysis, and will oversee and facilitate frequent interactions between the proposed TMC and other investigators, Cores and components of the SenNet Consortium.

总体TMC-项目摘要 细胞衰老是一种多面细胞命运，可阻止细胞增殖并激活合成 并分泌多种细胞因子，趋化因子，生长因子，蛋白酶和脂质，称为 衰老相关的分泌表型（SASP）。 SASP会影响组织微环境， 局部和远端，因此衰老细胞可以强烈影响组织功能。衰老细胞（SNC） 大多数脊椎动物（包括小鼠和人类）随着年龄的增长而增加，越来越清楚 通过遗传和药理操作，它们可以推动越来越多的与年龄相关的清单 病理学，从神经变性到癌症。目前，没有SNC的不变生物标志物 SNC的分子特性是明显的异质和可变的，具体取决于细胞和 组织类型，微环境，衰老诱导剂和时机。我们的总体目标是确定分子 在空间上，衰老细胞在人类中发生的时间和地点，以及它们的基因模式如何 表达和SASP随组织生理和年龄而变化。这些目标也是Sennet的目标 财团。因此，我们建议建立一个由一个由一个由一个组成的Sennet组织映射中心（TMC） 行政核心，生物传播核心，生物分析核心和数据分析核心。我们提出的TMC 将专注于三个人体组织（卵巢，乳房和骨骼肌）和三个生物流体（卵泡液， 血浆和尿液）。这些样品具有不同的生物学特征和细胞类型（体细胞和细胞类型 生殖；基质，上皮和脉管系统，随着年龄的增长而显示显着变化。所有材料都是 通过既定的合作，分包商和/或生物库（通过生物循环核心）获得。 他们的分析将包括最先进的转录组和蛋白质组学技术，这些技术将利用 几位Buck Institute调查人员的专业知识。我们的初步数据表明这些组织和生物流体 适合生物分析和数据分析核心中提出的最新技术， 以及我们随附的技术开发应用中提出的新技术（RFA-RM-- 21-009）。重要的是，我们的发现将适用于许多其他人体组织和生物流体 涵盖并补充较大的Sennet财团的整体目标。行政核心将 协调TMC的各个方面，从样本获取到分析，并将监督和促进 拟议的TMC与其他研究人员，核心和组件之间的频繁相互作用 Sennet财团。