Core 1: Human Cell Models of Aging Core

核心1：衰老核心的人体细胞模型

• 批准号: 10665581
• 负责人: FRED H GAGE
• 金额: $ 46.77万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10665581
• 关键词: 3-Dimensional; Adult; Age; Aging; Animal Model; Back; Bioenergetics; Biological; Biological Aging; Biology of Aging; Biometry; Blood; Body Composition; Cell Aging; Cell Communication; Cell Culture Techniques; Cell Line; Cell model; Cell physiology; Cells; Characteristics; Chronology; Clinical; Communities; Data; Data Set; Dermal; Educational workshop; Embryo; Epigenetic Process; Exhibits; Fibroblasts; Gene Expression Profile; Genetic Models; Goals; Heart; Heterogeneity; Human; Hybrid Cells; Hybrids; Image; Imaging technology; In Vitro; Individual; Kidney; Knowledge; Liver; Measures; Mitochondria; Modeling; Molecular; Molecular Profiling; Organ; Organoids; Pancreas; Participant; Phenotype; Physiological; Plasmids; Process; Protocols documentation; Punch Biopsy; Reagent; Rejuvenation; Research; Resource Sharing; Resources; Role; Sampling; Series; Shock; Skin; Smooth Muscle; Structure; System; Tissue Model; Tissues; Training; Work; age related; aged; biobank; biological research; cell repository; cell type; cohort; complex data; data streams; design; empowerment; experimental study; human model; human subject; human tissue; induced pluripotent stem cell; insight; lectures; machine learning algorithm; model organism; multiple omics; novel; novel strategies; open source; peripheral blood; phenotypic data; recruit; repository; research and development; stem cells; technology development; transgene expression; uptake

PROJECT SUMMARY – Human Cell Models of Aging Core The SD-NSC Human Cell Models of Aging Core (Human Cell Core) is focused on creating new cellular models of aging from human fibroblasts, including fibroblasts from a unique cohort representing the full breadth of adult chronological age and annotated for physical and functional measures of biological age. Genetic model organisms have long been important for aging research, but there are limitations to the extent to which animal models faithfully represent the molecular and cellular process of human aging. The overarching goal of this Core is to create powerful new human cell-based models to enable a wide range of studies into the molecular and cellular heterogeneities of human aging. Approaches for generating these new human models of aging draw largely from recent advances in creating induced cell types via the direct conversion of skin cell samples. Pioneering work from the Human Cell Core co-Lead, Dr. Gage, has shown that aging characteristics are maintained in these induced cell types. Pairing this approach with equally new approaches for creating 3D organoid cell cultures representative of different organ and tissue microenvironments, enables the creation of unprecedented human cell-based models of tissue aging. These models will enable robust analyses of cellular heterogeneities in human aging processes. As part of this effort, the Core will recruit human subjects ranging in age from 20–70+ years, thereby representing the full breadth of the healthy adult human age span. These participants will be extensively phenotyped for key clinical and physiological features of biological aging, and blood and skin samples will be collected. Skin samples will be used to derive primary dermal fibroblasts, from which both reprogrammed stem cells and directly induced cell types will be created and banked for sharing. The Human Cell Core will develop protocols for the direct inducement of different cell types and for the creation of organoids, including pancreas, kidney, liver, heart, smooth muscle, and vasculature. To promote the uptake of these new human cell models throughout the basic biology of aging research community, the Core will offer workshops and training sessions in conjunction with the Research Development Core. The protocols, specific reagents, and cells will be distributed to NSC affiliates directly from the Human Cell Core, and more broadly through open resources and cell repositories like the NIA Aging Cell Repository at the Coriell Institute and Addgene. Subject phenotype data will be shared along with the cell lines. Importantly, the Human Cell Core is designed to be integrated with the other Research Resource Cores of the SD-NSC, as human cell models (with subject-specific data) can be fed directly into the Heterogeneity of Aging Core for systems-level analysis of aging processes (multi-omic and advanced imaging). These complex datasets can then be fed into the Integrative Models of Aging Core for the application of new and existing integrative analyses. The Human Cell Core, as a stand-alone resource, and as an integrated component of the SD-NSC Core pipeline, will create substantial new opportunities to investigate the influences of cellular heterogeneity in human aging processes.

项目摘要 - 衰老核心的人体细胞模型 衰老核心（人细胞核）的SD-NSC人类细胞模型的重点是创建新的细胞模型 人类成纤维细胞的衰老，包括来自成人全部宽度的独特队列的成纤维细胞 按年代年龄和注释，用于生物年龄的物理和功能测量。遗传模型 长期以来对衰老研究一直很重要，但是有局限性的动物程度 忠实地代表人类衰老的分子和细胞过程。总体目标 核心是创建强大的基于人类细胞的新模型，以使大量研究成为分子 和人类衰老的细胞异质性。产生这些新的衰老模型的方法 在很大程度上源于最近通过皮肤细胞样品直接转化创建诱导细胞类型的进展。 人类细胞核心共同领导者Gage博士的开创性工作表明，衰老特征是 在这些诱导的细胞类型中保持。将这种方法与同样新的方法配对创建3D 代表不同器官和组织微环境的器官细胞培养物可以创建 前所未有的组织衰老的基于人类细胞的模型。这些模型将实现对细胞的强大分析 人衰老过程中的异质性。作为这项努力的一部分，核心将招募人类受试者 年龄从20-70岁以上，因此代表了健康的成人人类年龄跨度的全部广度。这些 参与者将被广泛表型，以用于生物衰老的关键临床和物理特征，以及 将收集血液和皮肤样本。皮肤样品将用于从原发性皮肤成纤维细胞中得出 将创建和库存用于共享的重编程干细胞和直接诱导的细胞类型。 人类细胞核将开发直接诱导不同细胞类型和创建的协议 包括胰腺，肾脏，肝脏，心脏，平滑肌和脉管系统的类器官。促进吸收 在衰老研究界的整个基本生物学中，这些新的人类细胞模型中，核心将提供 讲习班和培训课程与研究开发核心结合。协议，具体 试剂和细胞将直接从人类细胞核直接分布给NSC分支机构，更广泛地分布 通过开放的资源和细胞存储库，例如科里尔研究所的NIA老化细胞存储库和 addgene。主题表型数据将与细胞系共享。重要的是，人细胞核是 旨在与SD-NSC的其他研究资源核心集成为人类细胞模型 （具有特定于主题的数据）可以直接馈入系统级分析的老化核心的异质性 衰老过程（多词和高级成像）。然后可以将这些复杂的数据集送入 老化核心的集成模型用于应用新的和现有的集成分析。人类细胞 核心作为独立资源，作为SD-NSC核心管道的集成组成部分，将创建 大量新的机会来研究人类衰老过程中细胞异质性的影响。