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: 10540760
• 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/10540760
• 关键词: Acute Lung Injury; Affect; Angiopoietins; Animals; Architecture; Biological; Biology; Blood Vessels; 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; examination questions; experimental study; fibrotic lung; functional plasticity; injured; interest; interstitial; lung injury; lung repair; molecular marker; mortality; mouse model; novel; novel strategies; pathogen exposure; programs; repaired; response; restoration; segregation; 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.

抽象的 周细胞与许多器官的炎症和纤维化有关。数据来自 活化培养的肺周细胞的转录组分析揭示了多种 生物途径，包括炎症、血管生成过程和细胞迁移。目标 该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来描述肺细胞的命运 周细胞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 纤维化过程中源自周细胞和非周细胞来源的肌成纤维细胞的亚群 离体检查它们的功能差异。

项目成果

The Gut-Lung Axis: What's below the Diaphragm Is Also Important.

• DOI: 10.1165/rcmb.2022-0365ed
• 发表时间: 2022-12
• 期刊: American journal of respiratory cell and molecular biology
• 影响因子: 6.4

Angiopoietin-Like4 Is a Novel Marker of COVID-19 Severity.

• DOI: 10.1097/cce.0000000000000827
• 发表时间: 2023-01
• 期刊: Critical care explorations

Lung pericytes as mediators of inflammation.

• DOI: 10.1152/ajplung.00354.2022
• 发表时间: 2023-07-01
• 期刊: American journal of physiology. Lung cellular and molecular physiology

Endotoxin-induced acute lung injury in mice with postnatal deletion of nephronectin.

• DOI: 10.1371/journal.pone.0268398
• 发表时间: 2022
• 期刊: PloS one
• 影响因子: 3.7

Toll-interacting protein inhibits transforming growth factor beta signaling in mouse lung fibroblasts.

• DOI: 10.1096/fba.2023-00054
• 发表时间: 2024-01
• 期刊: FASEB bioAdvances
• 影响因子: 2.7