The Jackson Laboratory Senescence Tissue Mapping Center (JAX-Sen TMC)

杰克逊实验室衰老组织绘图中心 (JAX-Sen TMC)

• 批准号: 10683385
• 负责人: Ronny Korstanje
• 金额: $ 283.99万
• 依托单位: JACKSON LABORATORY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10683385
• 关键词: 3-Dimensional; Address; Adipose tissue; Age; Aging; Aloral; Antibodies; Atlases; Biological; Biological Aging; Biological Markers; Biology; Biology of Aging; Cancer Biology; Cancer Center; Cell Aging; Cell Nucleus; Cell physiology; Cells; Cellular biology; Chromatin; Chronic Disease; Clinical; Collaborations; Communities; Complement; Data; Data Analyses; Data Set; Databases; Dimensions; Disease; Elderly; Ensure; Environment; Face; Funding; Future; Gene Expression; Generations; Genetic; Genetic Variation; Goals; Health; Heart; Human; Hypothalamic structure; Image; Inbreeding; Individual; Informatics; Infrastructure; Intervention; Kidney; Knowledge; Laboratories; Leadership; Longevity; Maps; Metabolic; Methods; Mining; Modality; Modeling; Molecular; Morphology; Mus; Pancreas; Phenotype; Placenta; Positioning Attribute; Process; Proteins; Proteomics; Quality Control; Quantitative Trait Loci; RLK5-associated protein phosphatase; Reproducibility; Research; Resolution; Resources; Risk Factors; Role; Sample Size; Sampling; Shock; Site; Standardization; Syndrome; Techniques; Technology; The Jackson Laboratory; Therapeutic; Tissues; Transgenic Mice; Variant; Visualization; Work; advanced analytics; age related; aged; bioinformatics resource; clinically relevant; cohort; data integration; data mining; data standards; data tools; human tissue; image reconstruction; improved; innovation; interest; life history; lipidomics; mass spectrometric imaging; member; metabolomics; metadata standards; modifiable risk; mouse genetics; mouse genome; multimodality; multiple omics; novel; open data; phenome; programs; prospective; protein expression; senescence; synergism; technology development; tissue mapping; tissue reconstruction; transcriptome sequencing; transcriptomics; translational goal

PROJECT SUMMARY/ABSTRACT OVERALL The Jackson Laboratory (JAX) Cellular Senescence Network Mouse Tissue Mapping Center (JAX-Sen) represents a multi-modal interdisciplinary effort that draws upon existing, longstanding aging research programs at JAX, our role as a consortium site of KAPP-Sen, a funded SenNet human Tissue Mapping Center, and JAX’s close collaboration with UConn Health. JAX-Sen is organized around three cores nested in the well-resourced environment for aging research and multi-omics profiling at JAX. JAX-Sen will profile senescent cells in kidney, adipose tissue, placenta, pancreas, heart, and hypothalamus, selected for their clinical relevance to chronic diseases of aging, the domain expertise of the JAX-Sen leadership team in the biology of these tissues, and the overlap of four of the tissues with KAPP-Sen. We will leverage cutting-edge mouse resources including the Diversity Outbred, which offers unparalleled genetic diversity for modelling a range of molecular senescence phenotypes, and new inbred (C57BL/6J) transgenic mice that express p16 and p21 driven fluorescent tags to allow visualization enrichment for specific senescent cell subsets. The Biological Analysis Core will apply a multitude of analytical modalities to selected tissues (bulk and single cell and single nucleus RNAseq, Visium spatial transcriptomics, multiplexed antibody-based imaging, multiplexFISH, imaging mass spectrometry including lipidomics, metabolomics, proteomics, 3D tissue reconstruction from serial sections), and will re- evaluate these technologies throughout the project period to ensure our approaches align with those of other centers and that we maximally benefit from the technology development efforts in SenNet. These profiling activities will yield subcellular resolution of biomolecular content in senescent cells not possible with human samples, along with an expanded set of senescent cell biomarkers. The Data Analysis Core will combine robust computational capability with scalable and reproducible scientific workflows to develop and implement Network- wide open data and metadata standards. The Data Analysis Core will benefit from JAX’s unique mouse research resources to establish the diversity of senescence by integrating with expression quantitative trait locus and protein quantitative trait locus data in DO mice and JAX bioinformatics resources, e.g., Mouse Genome Informatics, Mouse Phenome Database, Monarch Initiative. The integrative mining of JAX-Sen data will lead to novel methods for multi-modal 3D map reconstruction from imaging data and will yield an important resource for SenNet interpretation and enrichment of human senescent cell data. Finally, the Administrative Core will provide strong oversight of project progress and nurture a culture of collaborative, dynamic scientific exchange within JAX-Sen. It will also maximize JAX-Sen’s engagement in the consortium through collaborative activities that will help optimize data generation activities and create new research synergies. In so doing, JAX-Sen will help achieve the goal of SenNet to generate a unprecedented atlas of mouse senescent cells and new biomarkers of senescence for human analysis and therapeutic application.

项目概要/总体摘要 杰克逊实验室 (JAX) 细胞衰老网络小鼠组织作图中心 (JAX-Sen) 代表了一种多模式跨学科的努力，借鉴了现有的、长期的老龄化研究项目 在 JAX，我们作为 KAPP-Sen（一家受资助的 SenNet 人体组织绘图中心）和 JAX 的联合网站发挥作用 与康涅狄格大学健康中心密切合作。 JAX-Sen 围绕嵌套在资源丰富的三个核心进行组织 JAX 的衰老研究和多组学分析环境。 JAX-Sen 将分析肾脏中的衰老细胞， 脂肪组织、胎盘、胰腺、心脏和下丘脑，根据其与慢性病的临床相关性而选择 衰老疾病、JAX-Sen 领导团队在这些组织生物学方面的专业知识以及 四个组织与 KAPP-Sen 重叠。我们将利用尖端的鼠标资源，包括 Diversity Outbred，为一系列分子衰老建模提供无与伦比的遗传多样性 表型，以及表达 p16 和 p21 驱动荧光标签的新型近交 (C57BL/6J) 转基因小鼠 允许对特定衰老细胞亚群进行可视化富集。生物分析核心将应用 针对选定组织的多种分析方式（批量、单细胞和单核 RNAseq、Visium 空间转录组学、多重抗体成像、多重FISH、成像质谱 包括脂质组学、代谢组学、蛋白质组学、连续切片的 3D 组织重建），并将重新 在整个项目期间评估这些技术，以确保我们的方法与其他方法保持一致 中心，我们可以从 SenNet 的技术开发工作中最大程度地受益。这些剖析 活动将产生衰老细胞中生物分子内容的亚细胞分辨率，这是人类不可能实现的 样本，以及一组扩展的衰老细胞生物标志物。数据分析核心将结合强大的 具有可扩展和可重复的科学工作流程的计算能力，用于开发和实施网络- 广泛开放的数据和元数据标准。数据分析核心将受益于 JAX 独特的小鼠研究 通过与表达数量性状基因座整合来建立衰老多样性的资源和 DO 小鼠中的蛋白质数量性状基因座数据和 JAX 生物信息学资源，例如小鼠基因组 信息学、小鼠表型数据库、Monarch Initiative。 JAX-Sen数据的综合挖掘将导致 从成像数据进行多模态 3D 地图重建的新方法，将为 SenNet 对人类衰老细胞数据的解释和丰富。最后，管理核心将提供 对项目进展进行强有力的监督，并在内部培育协作、动态的科学交流文化 JAX-参议员。它还将通过协作活动最大限度地提高 JAX-Sen 在联盟中的参与度，这些活动将 帮助优化数据生成活动并创造新的研究协同效应。这样做，JAX-Sen 将提供帮助 实现 SenNet 的目标，生成前所未有的小鼠衰老细胞图谱和新的生物标志物 衰老用于人类分析和治疗应用。