Biological Analysis Core

生物分析核心

• 批准号: 10556890
• 负责人: Darren Baker
• 金额: $ 101.17万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10556890
• 关键词: 3-Dimensional; ATAC-seq; Age; Aging; Algorithms; Atlases; Bioinformatics; Biological; Biological Assay; Blood; CDKN2A gene; Cell Aging; Cell Communication; Cells; Chronology; Classification; Computing Methodologies; Consensus; Cytometry; DNA Damage; Data; Data Analyses; Data Set; Detection; Ecosystem; Environment; Excision; Exhibits; Female; Flow Cytometry; Genomics; Goals; Hallmark Cell; Human; Image; Imaging technology; Infrastructure; Lamin B1; Longevity; Longitudinal Studies; Maps; Modality; Molecular; Mouse Strains; Mus; Nuclear; Pathology; Phenotype; Physiology; Plasma; Prevalence; Proteomics; RNA; Reporter; Research Personnel; Small Nuclear RNA; Suggestion; Time; Tissues; Transgenic Model; Transgenic Organisms; XCL1 gene; base; cell type; cellular imaging; epigenomics; experimental study; genetic signature; imaging modality; male; metabolomics; mouse model; multimodality; novel; programs; prospective; senescence; sex; single cell analysis; single cell technology; single-cell RNA sequencing; specific biomarkers; tissue resource; transcriptomics; transfer learning

The goal of the Biological Analysis Core (BAC) is to apply multi-modal single-cell and imaging technologies toward developing an Atlas of Senescence in Murine Tissues in male and female mice across the lifespan in multiple strains. Our team of aging and bioinformatics experts have extensive infrastructure and unique expertise that is ideally suited to build a comprehensive map of murine cellular senescence, including its regulators, cellular manifestations, and impact on cell communication within the tissue environment. To achieve this, we will develop an integrated pipeline for tissue analysis using genomic, imaging, and computational methods to characterize senescence with single-cell and/or spatial context. We will leverage the NIA Study of Longitudinal Aging in Mice (SLAM) multi-strain mouse aging project, transgenic reporter and senescence-depleted mice, and extensive single-cell datasets combined with novel transfer learning to yield cross-tissue identification of SnCs in plasma/serum and multiple select tissues (chosen due to the prevalence of SnCs, their association with aging- related pathologies in mice, and their inclusion in the Human SenNet Program). We propose the following Specific Aims, which encompass a multi-tiered approach to screen and deeply characterize SnCs in murine tissues across their lifespan: Aim 1: Establish multi-modal profiling of aging mice and transgenic models to identify cell senescence in murine tissues across lifespan and their impact on tissue physiology. Aim 2: Generate single-cell transcriptomic and epigenomic sequencing atlases of mouse aging to reveal tissue-specific SnC identities. Aim 3: Determine the impact of SnCs in tissues on their neighboring cell ecosystems using imaging- based phenotypic and spatial senescent mapping.

生物分析核心（BAC）的目标是应用多模式的单细胞和成像技术 在整个生命周期中的雄性和雌性小鼠的鼠组织中衰老的地图集 多种菌株。我们的衰老和生物信息学专家团队拥有广泛的基础设施和独特的专业知识 理想情况下适合构建鼠类细胞衰老的综合图，包括其调节剂，细胞 表现和对组织环境内细胞通信的影响。为了实现这一目标，我们将发展 使用基因组，成像和计算方法来表征组织分析的集成管道 具有单细胞和/或空间环境的衰老。我们将利用小鼠纵向老化的NIA研究 （SLAM）多晶体小鼠衰老项目，转基因记者和衰老的小鼠，并广泛 单细胞数据集与新型传输学习相结合，以产生SNC的跨组织识别 血浆/血清和多个选择组织（由于SNC的流行而选择，它们与衰老的关联 小鼠的相关病理及其纳入人类Sennet计划）。我们提出以下内容 具体目的，该目标包括一种多层屏幕方法，并深深地描述了鼠类中的SNC 整个寿命的组织： 目标1：建立老化小鼠和转基因模型的多模式分析以鉴定细胞衰老 在整个寿命的鼠组织中及其对组织生理的影响。 AIM 2：生成小鼠衰老的单细胞转录组和表观基因组测序图谱 揭示组织特异性的SNC身份。 AIM 3：使用成像 - 确定SNC在组织中对其相邻细胞生态系统的影响 - 基于表型和空间衰老映射。