Biological Analysis Core

生物分析核心

基本信息

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
项目类别：
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

项目摘要

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）的目标是应用多模态单细胞和成像技术旨在开发雄性和雌性小鼠整个生命周期的小鼠组织衰老图谱多种菌株。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非常适合构建小鼠细胞衰老的全面图谱，包括其调节因子、细胞衰老表现以及对组织环境内细胞通讯的影响。为了实现这一目标，我们将开发使用基因组、成像和计算方法来表征组织分析的集成管道单细胞和/或空间背景下的衰老。我们将利用 NIA 对小鼠纵向衰老的研究（SLAM）多品系小鼠衰老项目、转基因报告小鼠和衰老耗竭小鼠以及广泛的单细胞数据集与新颖的迁移学习相结合，可在中产生 SnC 的跨组织识别血浆/血清和多种选择的组织（由于 SnC 的普遍存在而选择，它们与衰老相关）小鼠的相关病理学及其纳入人类 SenNet 计划）。我们提出以下建议具体目标，包括采用多层方法筛选和深入表征小鼠中的 SnC 组织在其整个生命周期中：目标 1：建立衰老小鼠的多模式分析和转基因模型以识别细胞衰老整个生命周期中小鼠组织的变化及其对组织生理学的影响。目标 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 SnC 特性。目标 3：使用成像技术确定组织中 SnC 对其邻近细胞生态系统的影响基于表型和空间衰老图谱。