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

整体TMC -项目总结 细胞衰老是一个多方面的细胞命运，阻止细胞增殖并激活合成 和分泌大量的细胞因子、趋化因子、生长因子、蛋白酶和脂质， 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地影响组织功能。衰老细胞（SnCs） 在大多数脊椎动物中，包括小鼠和人类，随着年龄的增长， 通过遗传和药理学操作，他们可以驱动越来越多的与年龄有关的疾病， 病理学，从神经变性到癌症。目前，还没有稳定的SnCs生物标志物 并且SnCs的分子特征是显著异质和可变的，这取决于细胞和 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 在空间上，衰老细胞在何时何地出现在人类身上，以及它们的基因模式是如何变化的。 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组织映射中心（TMC）， 管理核心、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 将集中在三个人体组织（卵巢，乳房和骨骼肌）和三个生物流体（卵泡液， 血浆和尿）。这些样品具有不同的生物学特性和细胞类型（体细胞和 生殖;基质，上皮和脉管系统），显示出随年龄的显着变化。全部物料均 可通过已建立的合作、分包商和/或生物库（通过生物样本核心）获得。 他们的分析将包括尖端的转录组学和蛋白质组学技术， 几位巴克研究所调查员的专业知识我们的初步数据显示这些组织和体液 适用于生物分析和数据分析核心中提出的最新技术， 以及我们在附带的技术开发应用程序（RFA-RM）中提出的新技术， 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， 涵盖并补充更大的SenNet联盟的总体目标。行政核心将 协调TMC的所有方面，从标本采集到分析，并将监督和促进 拟议TMC与其他研究者、核心和组件之间的频繁互动 SenNet Consortium.

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.