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: 10045536
• 负责人: FRED H GAGE
• 金额: $ 34.36万
• 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/10045536
• 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; Complex; 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; Institutes; Kidney; Knowledge; Lead; Liver; Measures; Mitochondria; Modeling; Molecular; Molecular Profiling; Organ; Organoids; Pancreas; Participant; Phenotype; Physiological; Plasmids; Process; Protocols documentation; Punch Biopsy; Reagent; Research; Resource Sharing; Resources; Role; Sampling; Series; Shock; Skin; Smooth Muscle; Structure; System; Tissue Model; Tissues; Training; Work; age related; aged; base; biological research; cell repository; cell type; cohort; data streams; design; empowered; experimental study; human model; human subject; human tissue; induced pluripotent stem cell; insight; lectures; machine learning algorithm; 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.

项目概要-衰老核心的人类细胞模型 SD-NSC人类细胞衰老模型核心（Human Cell Core）专注于创建新的细胞模型 从人成纤维细胞，包括来自一个独特的队列，代表了整个宽度的成人成纤维细胞老化， 实际年龄和注释的生理和功能措施的生物年龄。遗传模型 长期以来，生物体对于衰老研究一直很重要，但动物在多大程度上受到限制， 模型忠实地反映了人类衰老的分子和细胞过程。这个项目的首要目标是 核心是创建强大的新的基于人类细胞的模型，以实现对分子生物学的广泛研究。 和人类衰老的细胞异质性。产生这些新的人类衰老模型的方法 主要来自于最近通过皮肤细胞样品的直接转化产生诱导细胞类型的进展。 人类细胞核心共同领导人盖奇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维持。将这种方法与同样新的3D创建方法相结合 代表不同器官和组织微环境的类器官细胞培养物， 前所未有的基于人体细胞的组织衰老模型。这些模型将使细胞的强大的分析， 人类衰老过程中的异质性作为这项工作的一部分，核心将招募人类受试者， 年龄从20-70+岁，从而代表健康成年人年龄跨度的全部宽度。这些 参与者将被广泛表型生物老化的关键临床和生理特征， 将采集血液和皮肤样本。皮肤样品将用于衍生原代真皮成纤维细胞， 这两个重编程的干细胞和直接诱导的细胞类型将被创建和储存用于共享。 人类细胞核心将开发用于直接诱导不同细胞类型和创建 包括胰腺、肾脏、肝脏、心脏、平滑肌和脉管系统。为了促进 这些新的人类细胞模型在整个基础生物学衰老研究社区，核心将提供 研讨会和培训课程与研究开发核心。协议，具体 试剂和细胞将直接从人类细胞中心分发给国家科学中心的附属机构， 通过开放资源和细胞库，如Coriell研究所的NIA老化细胞库， Addgene受试者表型数据将与细胞系一起沿着。重要的是，人类细胞核心是 旨在与SD-NSC的其他研究资源核心集成，作为人类细胞模型 (with特定对象的数据）可以直接输入到老化核心异质性中进行系统级分析 衰老过程（多组学和先进成像）。然后，这些复杂的数据集可以被馈送到 老化核心综合模型，用于新的和现有的综合分析。所述人类细胞 核心，作为一个独立的资源，并作为SD-NSC核心管道的集成组件，将创建 研究细胞异质性在人类衰老过程中的影响的新机会。