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 细胞衰老是一种多方面的细胞命运，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 衰老相关分泌表型（SASP）。 SASP 可以影响组织微环境， 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，这一点越来越清楚 通过遗传和药理学操作，它们可以驱动越来越多的与年龄相关的疾病 病理学，范围从神经变性到癌症。目前，SnCs尚无不变的生物标志物 SnC 的分子特征非常异质且可变，具体取决于细胞和 组织类型、微环境、衰老诱导物和时间。我们的总体目标是从分子水平上确定 在空间上，人类衰老细胞发生的时间和地点，以及它们的基因模式如何 表达和 SASP 随组织生理学和年龄而变化。这些目标也是SenNet的目标 财团。因此，我们建议建立一个 SenNet 组织绘图中心 (TMC)，其中包括 行政核心、生物样本核心、生物分析核心和数据分析核心。我们建议的TMC 将重点关注三种人体组织（卵巢、乳房和骨骼肌）和三种生物液体（卵泡液、 血浆和尿液）。这些样本具有独特的生物学特征和细胞类型（体细胞和 生殖；基质、上皮和脉管系统）随着年龄的增长而发生显着变化。所有材料均为 通过已建立的合作、分包商和/或生物库（通过生物样本核心）提供。 他们的分析将包括尖端的转录组学和蛋白质组学技术，这些技术将利用 几位巴克研究所研究人员的专业知识。我们的初步数据表明这些组织和生物体液 适合生物分析和数据分析核心中提出的最先进的技术， 以及我们随附的技术开发申请 (RFA-RM- 21-009）。重要的是，我们的研究结果将适用于许多其他人体组织和生物体液，以便 包含并补充更大的 SenNet 联盟的总体目标。行政核心将 协调 TMC 的各个方面，从样本采集到分析，并将监督和促进 拟议的 TMC 与其他研究者、核心和组成部分之间的频繁互动 森网联盟。