Application of single-cell trajectory analysis in single-cell transcriptomics to elucidate the biology of lung pericytes in injury, repair, and regeneration

单细胞轨迹分析在单细胞转录组学中的应用阐明肺周细胞在损伤、修复和再生中的生物学

• 批准号: 10340848
• 负责人: Chi F Hung
• 金额: $ 8.83万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10340848
• 关键词: ANGPTL4 gene; Acute Lung Injury; Affect; Angiopoietins; Animals; Architecture; Biological; Biology; Cell physiology; Cells; Cicatrix; Cluster Analysis; Complex; Data; Disease; Embryonic Development; Endothelium; Fibrosis; Gene Expression Profile; Generations; Genetic Transcription; Goals; Grant; Heterogeneity; Immune; In Vitro; Inflammation; Inflammatory Response; Injury; Kidney; Lead; Lung; Maintenance; Mediating; Methods; Molecular Profiling; Morbidity - disease rate; Muscle; Myofibroblast; Natural regeneration; Organ; Pathway interactions; Pericytes; Phase; Phenotype; Population; Process; Pulmonary Fibrosis; Regulation; Research Personnel; Resolution; Role; Skin; Stimulus; Stromal Cells; Surface; Universities; Up-Regulation; Vascular Diseases; Washington; Work; angiogenesis; cell motility; cell regeneration; cell type; experimental study; fibrotic lung; functional plasticity; injured; injury and repair; interest; interstitial; lung injury; lung repair; molecular marker; mortality; mouse model; novel; novel strategies; pathogen exposure; programs; repaired; response; restoration; tissue injury; transcriptome sequencing; transcriptomics; vasculogenesis

ABSTRACT Pericytes have been implicated in inflammation and fibrosis in a number of organs. Data from transcriptomic analyses of activated cultured lung pericytes reveal upregulation of multiple biological pathways including inflammation, angiogenic processes, and cell migration. The goal of this project is to understand the functional plasticity of lung pericytes throughout injury and in lung repair. We are interested in how lung pericytes modulate lung repair in lung fibrosis through angiogenesis and myofibroblast differentiation. In Aim 1, we propose to use state-of-the-art single cell trajectory analysis on single-cell transcriptomic data to describe the cell fate of lung pericytes from acute lung injury to fibrosis. In Aim 2, we propose to study selected stromal subpopulations derived from pericytes and non-pericyte-derived myofibroblasts during fibrosis to examine their functional differences ex vivo.

摘要 周细胞与许多器官的炎症和纤维化有关。数据从 活化培养的肺周细胞的转录组学分析揭示了多个 生物学途径，包括炎症、血管生成过程和细胞迁移。目标 本项目的目的是了解肺周细胞在整个损伤过程中的功能可塑性， 肺修复我们感兴趣的是肺周细胞如何通过调节肺纤维化中的肺修复， 血管生成和肌成纤维细胞分化。在目标1中，我们建议使用最先进的 对单细胞转录组数据进行单细胞轨迹分析，以描述肺的细胞命运 从急性肺损伤到纤维化在目标2中，我们建议研究选定的基质 在纤维化过程中衍生自周细胞和非周细胞衍生的肌成纤维细胞的亚群， 检查它们离体的功能差异。