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Identifying niche factors regulating distinct properties of AT2 stem cells

识别调节 AT2 干细胞独特特性的生态位因子

基本信息

批准号：
9767857
负责人：
Tushar Jasubhai DESAI
金额：
$ 54.39万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-22 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9767857
关键词：
3-Dimensional Ablation Acute Adult Respiratory Distress Syndrome Aging Alveolar Automobile Driving Binding Biochemistry Bronchoscopy Cell Death Cell Proliferation Cell Transplantation Cell Transplants Cell division Cells Chronic Chronic Obstructive Airway Disease Cues Data Diagnosis Disease Disease Progression EGF gene Elderly Environment Epidermal Growth Factor Receptor Epithelial Epithelial Cells Failure Fibroblasts Fostering Functional disorder Gases Goals Growth Human Immune Injury Integrins Knowledge Lead Learning Life Ligands Longevity Lung Lung Capacity Lung diseases Maintenance Maps Medical Minor Mitogens Modeling Molecular Morbidity - disease rate Mus Natural regeneration Organ Paracrine Communication Pathology Patients Pharmacology Pneumonia Population Production Proliferating Property RNA Regulation Research Resolution Respiratory Failure Respiratory physiology Role Signal Pathway Signal Transduction Signaling Molecule Site Smoking Stem cells Surface Testing Therapeutic Time Tissues Transplantation WNT Signaling Pathway Work alveolar type II cell autocrine base cell behavior cell injury dimer idiopathic pulmonary fibrosis improved in vivo injured lung injury lung regeneration mortality new technology novel paracrine prevent programs receptor reconstitution repaired resilience response response to injury single cell analysis single cell technology stem cell biology therapeutic development

项目摘要

PROJECT SUMMARY A number of serious respiratory diseases cause problems with gas exchange, which is the principal function of the lungs. Some of these are sudden in onset, like lung injury from a severe pneumonia, while others develop over long periods of time, like COPD and Idiopathic Pulmonary Fibrosis (IPF). There is some evidence that the chronic forms of respiratory failure result from loss of the capacity of the lungs to maintain themselves, in part due to dysfunction of resident lung stem cells that normally perform this role. Therefore, discovering the specific molecular and cellular mechanisms by which lung stem cells are regulated throughout life may be helpful for understanding how COPD and IPF develop. Achieving this deep level of understanding about lung stem cell regulation may lead to improved strategies to predict, diagnose, and even pharmacologically treat such diseases. Furthermore, given the easy accessibility of the lung via medical bronchoscopy, it is an ideal organ to target with the delivery of healthy stem cells that might prevent disease progression or even produce improvement if they can be successfully transplanted into diseased lungs. We have found that one of the functional cells in the gas exchange region, the alveolar type II (AT2) cell, acts as a stem cell for mouse lung throughout the lifespan, and identified several factors that regulate its activity. The AIMS of this proposal are to expand our understanding of how these stem cells are regulated by studying the local environment that provides the signals that control their activity, including proliferation and differentiation. We will investigate three specific and distinct aspects of the stem cell behavior, including how it is induced to proliferate to generate new cells, how it attains the capacity to transiently regulate itself in response to injury, and whether the regulatory environment is as or more important than the stem cell itself for maintaining the lungs over the lifespan. Our findings will significantly deepen our understanding of precisely how these lung stem cells can be deliberately manipulated to generate large numbers suitable for cell transplantation, or by pharmacologically driving their activity for therapeutic 're-growth' purposes.

项目总结